bluuebunny/crossref_metadata_2025 huggingface dataset:
Provocation of Postural Hypotension by Insulin in Diabetic Autonomic Neuropathy
Authors: Page M McB , Watkins P J
Published: September 2013

The effect of insulin administration on blood pressure has been investigated in eight diabetes with autonomic neuropathy. Systolic and diastolic pressures fell considerably after insulin in all of them. This effect was aggravated by tilting to the vertical position. Five patients fainted when upright with systolic blood pressures less 50 mm. Hg.

This hypotensive effect of insulin occurs whether it is administered intravenously, intramuscularly, or subcutaneously. The onset of the effect is almost immediate after intravenous insulin, is progressive, and may last for several hours. It coincides with a falling blood glucose level and occurs before hypoglycemic levels are reached, and it may be present when the blood glucose level is still elevated. Diurnal variations of postural hypotension have been recorded in some patients, the standing blood pressure falling with the onset of insulin action and rising again as the latter declines.

Some of our patients were unable to differentiate between symptoms of hypoglycemia and hypotension. Postural hypotension may account for some episodes of sudden loss of consciousness without warning, usually attributed to hypoglycemia.
Effect of Streptozotocin on Red-blood-cell-reduced Glutathione: Modification by Glucose, Nicotinamide, and Epinephrine
Authors: Slonim A E , Fletcher T , Burke V , Burr I M
Published: September 2013

Previous studies had shown that administration of streptozotocin to rats produces both diabetes and hemolysis and that both could be ameliorated by prior injections of diazoxide. Thus, it appeared pertinent to define the effect of streptozotocin on the red cell. In the present studies, streptozotocin administered in vivo to rats produced a rapid fall in red-cell-reduced glutathione. This effect was duplicated in vitro in incubated human red cells. Furthermore, it was demonstrated that glucose loading prior to bleeding modified the in-vitro red-cell GSH response to streptozotocin and that preincubation of red cells from fasted individuals with glucose, nicotinamide, and epinephrine (but not nicotinic acid) protected against the subsequent effect of streptozotocin on RBC GSH. The pattern of the RBC GSH response under each of these conditions is that which occurs in response to challenge with an oxidant, that is, with appropriate protection, oxidation stress produces an acute rise rather than falll in gsh. further, when glucose was present through both preincubation and test periods (i.e., in presence of streptozotocin) a third pattern of GSH response was observed–no change. The data are compatible with the postulate that the cytotoxic action of streptozotocin is dependent, in part, on an oxidant effect, and that glucose may protect through at least two mechanisms, that adrenergic stimulation can enhance protective mechanisms against redox insults and so contribute to maintenance of cell viability.
Hemoglobin AIc as an indicator of the degree of glucose intolerance in diabetes
Authors: Koenig Ronald J , Peterson Charles M , Kilo Charle , Cerami Anthony , Williamson Joseph R
Published: September 2013

Hemoglobin AIc concentration, fasting blood sugar, response to an oral glucose tolerance test, and skeletal muscle capillary basement membrane thickness were measured in diabetic patients. Hemoglobin AIc concentration correlates with both response to a glucose tolerance test (r = 0.82, p < 0.001) and fasting blood sugar (r = 0.62, p < 0.001). The correlation of hemoglobin AIc concentration with glucose tolerance is independent of fasting blood sugar concentration (partial r = 0.61, p < 0.005), whereas that of hemoglobin AIc with fasting blood sugar probably reflects the relationship between fasting blood sugar levels and glucose tolerance (partial r = 0.22, p < 0.05). Hemoglobin AIc levels do not correlate with basement membrane thickness (r = 0.15, p < 0.05).
Glucose Tolerance and Insulin Release, A Mathematical Approach: II. Approximation of the Peripheral Insulin Resistance After Oral Glucose Loading
Authors: Sluiter W J , Erkelens D W , Terpstra P , Reitsma W D , Doorenbos H
Published: September 2013

A parameter of peripheral insulin activity (A = 10(4)/IpGp) can be obtained after oral glucose loading by simple calcuation using insulin and glucose levels at the glucose peak. In combination with a glucose-independent parameter of beta-cell function (CIR = 100· I/G(G-70) a parameter of glucose tolerance (GT = A · CIR) is defined. The parameters allow one to separate the contributions of beta-cell function and peripheral insulin resistance to the glucose tolerance observed after glucose loading. Examples, based on the literature and our own work, illustrate the increase of A and GT by cortisone acetate premedication as well as long-term oral contraceptive medication.
Vascular Reactivity to Angiotensin II and to Norepinephrine in Diabetic Subjects
Authors: Christlieb A Richard , Janka Hans-Uwe , Kraus Barbara , Gleason Ray E , Icasas-Cabral Esperanza A , Aiello Lloyd M , Cabral Bienvenido V , Solano Alberto
Published: September 2013

Vascular responsiveness to infused angiotensin II and to norepinephrine was determined in 14 normal subjects and two groups of diabetic subjects, 16 with no clinically detectable diabetic complications and 14 with diabetic retinopathy but no clinical evidence of nephropathy. All were maintained on a 100-mEq.-Na-100-mEq.-K diet. Serum electrolytes, 24-hour urinary sodium, creatinine clearance, and plasma renin activity did not differ significantly among the groups. Group mean baseline diastolic pressure in those with retinopathy was higher than in normal subjects but no significantly different from that of uncomplicated diabetics. The pressor dose of angiotensin II (ng./kg./min. to increase diastolic blood pressure 20 mm. Hg) for each group respectively was 11.5 ± 0.9, 12.9 ± 1.3, and 8.3 ± 1.3, and the slope of the dose-response curve (mm. Hg rise in blood pressure resulting from the infusion of 1 ng./kg./min. following the initial increment in blood pressure) was 2.0 ± 0.2, 1.6 ± 0.2, 3.3 ± 0.6. For norepinephrine, the pressor doses were 163 ± 24, 212 ± 21, and 123 ± 11 and slopes were 0.17 ± 0.03, 0.13 ± 0.02, and 0.20 ± 0.02. Neither diabetic group differed significantly from normal subjects. Diabetics with retinopathy were more sensitive to angiotensin II, pressor dose (P < 0.059) and slope (P < 0.02), and to norepinephrine, pressor dose (P < 0.006) and slope (P =0.05) than those without complications. These data suggest that vascular reactivity is enhanced in diabetics with retinopathy.
Aging Changes in Intervertebral Discs and Spondylosis in Chinese Hamsters
Authors: Silberberg Ruth , Gerritsen George
Published: September 2013

Vertebrae and intervertebral discs of Chinese hamsters, a species of rodents that develop spontaneous diabetes, were investigated for age-linked changes and for the occurrence of spondylosis. Aging changes in the intervertebral discs were similar in diabetic and nondiabetic animals. The incidence of spondylosis was significantly increased and its onset was accelerated in the diabetic animals. The mechanisms operative in the pathogenesis of the lesions and their relation to the human disease are discussed.
Long-term Perfusion of Isolated Rats Islets in Vitro
Authors: Lacy Paul E , Finke Edward H , Conant Susan , Naber Stephen
Published: September 2013

A perfusion system is described for long-term maintenance of isolated rat islets in vitro. This system permits the monitoring of the pattern, rate, and amount of insulin secretion following repeated, acute stimulations with glucose during the period of culture. Fibroblastic proliferation did not occur, thus making is possible to reclaim the islets for biochemical and morphologic studies at the conclusion of the experiments. Maintenance of the islets with a low concentration of glucose (1.0 mg./ml.) resulted in a marked decline in insulin secretion following acute stimulations with glucose (5.0 mg./ml.) during an eight-day interval. Stimulation with 10 mM theophylline and 5.0 mg./ml. glucose on day 9 resulted in enhanced insulin release. The decline in glucose sensitivity occurred even more rapidly when the islets were maintained in the presence of a lower concentration of glucose (0.5 mg./ml.). The pattern of insulin release was altered with an absence of a first phase of secretion. Adenylate cyclase activity of islets maintained with 0.5 mg./ml. glucose for four days was significantly decreased in comparison with islets from fed rats and islets maintained with 2.5 mg./ml. glucose. A means of maintaining the same biphasic pattern and amount of glucose-induced insulin release was achieved by using alternating levels of glucose (1.5 and 2.5 mg./ml) for maintenance of the islets during a 36-day interval.
Diabetes Mellitus in American Indians—Standards for Diagnosis and Management
Authors: Sievers Maurice L
Published: September 2013

In most American Indian tribes the frequency of diabetes mellitus is much > among the non-Indians, and surveillance of health records has shown that many types of illnesses occur more often in the diabetics than in the nondiabetics. Standards, or guidelines, have been developed for diabetes detection and treatment for purposes of limiting diabetes diagnoses to persons with high probabilities of having the disease and concentrating diabetes case finding among high-risk groups or individuals. The guidelines emphasize that early diagnosis and careful management of diabetic pregnancies can decrease rates of macrosomia, congenital malforamtions, spontaneous abortion, stillbirth, and neonatal death. Diabetes management is based on staging criteria and requires trained paramedical workers in many aspects of management of asymptomatic diabetics, while the physicians concentrate more extensively on diabetes with symptoms and remediable complications.
Carbohydrate Metabolism and Capillary Basement-membrane Thickness in Children: I. Cross-sectional Studies
Authors: Sheikholislam Bagher M , Mas Julian J , Lin Hung-Jung , Lowrey George H , Stephenson Steve R , Peterson Gregory E , Devereux Dennis F , Volk Thomas L
Published: September 2013

Thirty-nine children from three to 16 years of age were included in this study. Nineteen were diabetics, seven were “suspected” diabetics (with evidence of glucose intolerance but without repeated fasting hyperglycemia), and 13 were controls. Mean glucose disappearance rates (K) during intravenous glucose tolerance tests (IVGTTs) were 2.19 for the controls, 1.23 for the suspected diabetics, and 0.70 for 14 diabetics tested; the differences were statistically significant. Diabetics had the smallest and suspected diabetics the greatest plasma insulin responses during IVGTTs. Fasting plasma growth hormone (GH) varied widely. GH generally decreased or remained unchanged during IVGTTs, but two diabetics exhibited slight increases and two suspected diabetics pronounced increases.

Basement-membrane thickness (BMT) was examined in 42 quadriceps femoris needle biopsies. Average BMT (ABMT) and minimum BMT (MBMT) correlated well (r = 0.91). BMT did not correlate well with age or, in the diabetics, with duration of clinical disease. Diabetics had the greatest and controls the least mean ABMT and MBMT, but the differences were not statistically significant. High values (those exceeding mean control values by more than two standard deviations) were much more common among the suspected diabetics and the diabetics. One of 13 controls, three of six suspected diabetics, and six of 19 diabetics had high ABMT values; two suspected diabetics and five diabetics had high MBMT values. Correlations between BMT and K were negative for the most part, but correlation coefficients were small. Serial studies in four of the children suggest that BMT and glucose tolerance tend to change in opposite directions.
Effect of Diabetes Mellitus and Insulin on the Turnover and Metabolic Response to Ketones in Man
Authors: Sherwin Robert S , Hendler Rosa G , Felig Philip
Published: September 2013

To determine the effect of diabetes mellitus on ketone removal rates, Na DL-β-hydroxybutyrate was administered as a continuous three-hour infusion (3 mg./kg./min.) to healthy volunteers and insulin-dependent diabetics in the postabsorptive state. An additional group of healthy controls received intravenous glucose (50 gm.) or glucose and insulin during the ketone infusion to determine the effect of hyperinsulinemia on ketone removal.

Following ketone infusion, total blood ketone levels in the diabetics were twofold greater than in controls (p < 0.001). The metabolic clearance rate of ketones (MCRk) in the diabetics was reduced by 4per cent from that of controls (p < 0.001). In contrast, the calculated production rate of ketones (PRk) in diabetics was not consistently different from that observed in controls. In diabetics with normal PRk, MCRk remained significantly below control values (p < 0.001).

The ketone infusion resulted in a fall in plasma glucose and alanine levels in the normals as well as diabetics. However, the decline in plasma glucose induced by the ketone infusion was five- to sixfold greater in the diabetics than in controls (p < 0.005) and correlated linearly with the decline in plasma alanine (p < 0.02).

Administration of intravenous glucose during an ongoing ketone infusion in normal subjects resulted in 37 ± 5 per cent reduction in β-hydroxybutyrate, but no change in acetoacetate concentration. The decline in β-hydroxybutyrate was two- to threefold greater than would be expected if glucose had acted solely to inhibit endogenous ketone production. Similar results were observed when hyperinsulinemia without hyperglycemia was produced by simultaneous administration of insulin and glucose.

It is concluded that (1) ketone disposal is reduced in diabetes even when ketone production is normal, suggesting the rate of ketone utilization may be a more sensitive index of insulin deficiency than is ketone production; (2) hyperinsulinemia stimulates β-hydroxybutyrate utilization without influencing acetoacetate concentration; and (3) increased blood ketone levels induced by infusion of Na DL-β-hydroxybutyrate reduce plasma glucose and alanine concentrations in diabetes. These findings thus support a role for insulin in influencing ketone disposal in normal as well as diabetic man and a role for ketones in influencing substrate availability for gluconeogenesis in diabetes.
Quantitation of Human Pancreatic Beta-cell Function by Immunoassay of C-Peptide in Urine
Authors: Horwitz David L , Rubenstein Arthur H , Katz Adrian I
Published: September 2013

Human proinsulin connecting peptide (C-peptide) was measured by immunoassay in urine from 25 normal subjects, 18 patients with diabetes mellitus, and 34 patients with various degrees of renal insufficiency. Assay validation studies showed that pancreatic C-peptide was quantitatively recovered when added to urine. Fractionation of urine by gel filtration indicated that most endogenous C-peptide eluted in fractions that corresponded to the C-peptide standard.

In 34 nondiabetic subjects with normal kidney function or various renal diseases, C-peptide clearance was independent of creatinine clearance over a range of 6 to 190 ml./min. Urine C-peptide clearance (5.1 ± 0.6 ml./min.) is greater than that of insulin (1.1 ± 0.2 ml./min.), and the total quantity of C-peptide excreted in the urine per day represents 5 per cent of pancreatic secretion, as against only 0.1 per cent of secreted insulin.

Healthy subjects excreted 36 ± 4 μg. C-peptide per 24 hours, while this value in juvenile-onset diabetics was only 1.1 ± 0.5 μg. Adult-onset diabetics excreted 24 ± 7 μg./24 hr., the range overlapping the excretory rates of both normal subjects and juvenileonset diabetics. Two insulin-requiring adult-onset diabetics showed significant beta-cell reserve during the course of acute infections.

These results suggest that urine C-peptide provides a useful means of assessing beta-cell secretory capacity over a period of time and is especially advantageous when frequent blood sampling is not feasible.
Measurement of Antidiabetic Sulfonylureas in Serum by Gas Chromatography with Electron-capture Detection
Authors: Braselton W Emmett , Bransome Edwin D , Huff Thomas A
Published: September 2013

A method is described for measurement of chlorpropamide, tolbutamide, and the tolbutamide metabolites hydroxymethyltolbutamide and carboxytolbutamide in blood. It consists of formation of the thermally stable methyl-trifluoroacetyl derivatives of chlorpropamide and tolbutamide, and the methyl-heptafluorobutyryl derivatives of hydroxymethyltolbutamide and carboxytolbutamide, which are then analyzed by electron-capture gas chromatography. Measurements of blood levels of the compounds with this method have been verified by quantitation of the same samples using gas chromatography-mass spectrometry in the mass fragmentography mode. Blood level values and β-phase half-time disappearance rates of chlorpropamide, tolbutamide, hydroxymethyltolbutamide, and carboxytolbutamide were measured in normal volunteers following an oral dose of chlorpropamide or tolbutamide. Blood levels of the four compounds were also determined in a few diabetics receiving continuous daily treatment.
Effect of Somatostatin on Meal-stimulated Pancreatic Exocrine Secretions in Dogs
Authors: Wilson Robert M , Boden Guenther , Shore Laurence S , Essa-Koumar Noorjehan
Published: September 2013

The effect of exogenously administered somatostatin (SRIF) on meal-stimulated secretions of the exocrine pancreas was studied in dogs with chronic pancreatic Fistulas. Dogs were fed 600 gm. of raw meat, and pancreatic output of water, bicarbonate, and protein was measured. Bicarbonate and protein secretions rose markedly postfeeding in all control animals. Four hundred micrograms or 100 μg. of SRIF infused for one hour together with a meal completely prevented the postfeeding rise in pancreatic secretions. SRIF (100 μg./hr.) infused one hour after a meal suppressed pancreatic secretions to basal levels within 30 minutes. Pancreatic secretions rose promptly after discontinuation of SRIF in all dogs. These data indicate (1) SRIF completely prevents pancreatic bicarbonate and enzyme responses when given together with a meal; (2) it completely suppresses already initiated pancreatic responses when given one hour after a meal; (3) 100 μg. of SRIF is as effective as 400 μg. in suppressing the postprandial rise in pancreatic secretions. We conclude that SRIF severely interferes with pancreatic secretions during normal alimentation and that this observation should be considered if SRIF is to be used as a therapeutic agent.
On the Mechanism of Diazoxide-induced Hyperglycemia
Authors: Altszuler Norman , Hampshire Jennifer , Moraru Ety
Published: September 2013

Infusion of diazoxide (16.5 mg./kg. in 10 minutes) into normal unanesthetized dogs resulted in a prompt hyperglycemia due to increased hepatic glucose production as measured with a 3-3H-glucose primer-infusion technique. Plasma insulin and gtucagon were decreased. Glucose uptake failed to increase. Diazoxide administration during period of alpha adrenergic receptor blockade with phentolamine still caused hyperglycemia and increased glucose production. Glucose uptake was inhibited despite adequate plasma insulin. Infusion of somatostatin along with insulin prevented the effects of diazoxide on plasma glucose and glucose production.

It is concluded that diazoxide hyperglycemia is not due solely to decreased insulin secretion or increased epinephrine secretion and that gtucagon is not a contributory factor. Diazoxide may act directly to increase glucose production and inhibit glucose uptake. Somatostatin appears capable of blocking the effect of diazoxide on glucose production by an unknown mechanism.
Measurement of “True” Glucose Production Rates in Infancy and Childhood with 6,6-Dideuteroglucose
Authors: Bier Dennis M , Leake Rosemary D , Haymond Morey W , Arnold Kenneth J , Gruenke Larry D , Sperling Mark A , Kipnis David M
Published: September 2013

“New” glucose production has been measured in 54 infants and children for the first time by continuous three-to-four-hour infusion of the safe, nonradioactive tracer 6,6-dideuterogiucose. The use of combined gas chromatography-mass spectrometry with monitoring of selected ions allowed deuterium enrichment in blood glucose to be measured on microliter samples with an error of less than 2 per cent. In the young child, glucose production increased in a slightly curvilinear manner from 1 kg. to 25 kg. body weight, when it reached 140 mg. per minute, almost the adult value of 173 mg. per minute (2.28 ± 0.23 mg./kg. ·min., mean ± S.E.). Normalized for weight, glucose production in premature infants was 5.46 ± 0.31 mg./kg. ·min., in term neonates averaged 6.07 ± 0.46 mg./kg. · min., in children below the age of six years was 7.1 ± 0.27 mg./kg.· min., and in late childhood averaged 5.4 ± 0.28 mg./ kg.· min. Relative to estimated brain weight, however, glucose production was essentially linear from the 1-kg. premature infant to the 80-kg. adult. These data, the first measurements of “new” glucose production in childhood, suggest that brain size may be a principal determinant of those factors that regulate hepatic glucose output throughout life.
Oral Contraceptive Use and Other Factors in the Standard Glucose Tolerance Test
Authors: Wingerd John , Duffy Thomas J
Published: September 2013

Three-hour standard glucose tolerance tests were performed on 2,248 women subjects with a family history of diabetes.

Use of oral contraceptives (OCs) was associated with equal elevations in one- and two-hour values but, surprisingly, lowered fasting blood sugars. A similar but weaker trend was present for other estrogen use.

Increasing age correlated with higher blood glucose values at all time points of the test, most markedly at one hour. Increasing relative weight was also associated with increased values at all hours of the test; here the increase was most marked (and approximately equal) at one and two hours. The rise in glucose, however, remained relatively well sustained at three hours, in contrast to most other variables. Glycosuria in overweight women was accompanied by a greater degree of hyperglycemia than in lean subjects.

A history of first-degree diabetic relatives tended to be associated with elevated values at all time points, but only at the fasting and one-hour points were the values significantly higher than those of women with lesser degrees of diabetic relationship. History of cholecystectomy was also associated with elevated glucose levels.

Heavy drinkers had a high one-hour mean, with normal to low two- and three-hour tests; smoking was not associated with any differences at the fasting or one-hour points, but smokers showed significantly decreased levels at two and three hours.

Principal-components analysis showed that fasting level, the “area under the curve,” and the steepness of descent from the one-hour level were completely independent aspects of the glucose tolerance test curve and could be used to summarize the original four data points of the test.
The Use, in Diabetic Rats and Monkeys, of Artificial Capillary Units Containing Cultured Islets of Langerhans (Artificial Endocrine Pancreas)
Authors: Sun Anthony M , Parisius Wolf , Healy George M , Vacek I , Macmorine Hilda G
Published: September 2013

A unit was constructed that consisted of a core of hollow fibers through which low-molecular-weight substances, such as glucose and insulin, could pass freely but were impermeable to high-molecular-weight proteins, such as antibodies. Islets of Langerhans from normal rats were planted in the space surrounding the fibers, and either blood or nutrient medium was circulated through the fibers themselves. In experiments with animals, the units were attached to the vascular system of diabetic rats and monkeys. Blood glucose concentrations in the rats were reduced to nondiabetic levels within one hour and were maintained for the duration of the experiments. In monkeys the blood glucose level declined from 210 mg./100 ml. to 90 mg./100 ml. in four hours and insulin in the serum rose to 93 μU./ml. in one-half hour. Also, we have found that islets from monkeys cultivated in the artificial endocrine pancreas (AEP) continue to release insulin into circulating tissue culture medium for over eight months.
Morphometric Quantitation of the Pancreatic Insulin-, Glucagon-, and Somatostatin-positive Cell Populations in Normal and Alloxan-diabetic Rats
Authors: McEvoy Robert C , Hegre Orion D
Published: September 2013

The pancreatic insulin-, glucagon-, and somatostatin-positive cell populations were quantitated in normal and alloxan-diabetic rats. The method of quantitation (linear scanning) allowed an estimation of absolute changes in these cell populations through 14 months of diabetes. The changes in cell masses were correlated with changes in plasma and pancreatic immunoreactive insulin and glucagon. A marked reduction in the insulin-positive beta cells was demonstrated within seven days after alloxan treatment. No significant change in the glucagon-positive alpha cell population was noted in the diabetic rats when compared with normoglycemic controls. A statistically significant increase in the pancreatic somatostatin-positive delta cell population was demonstrable only after 14 months of alloxan diabetes. The results would suggest that the hyperglucagonemia of insulin-deficient diabetes is not a consequence of an increased pancreatic alpha cell population. In addition, since the increase in the pancreatic delta cell mass was found only late in the course of alloxan diabetes in the rat, the increase in delta cells is probably not of significance in the pathophysiology of diabetes in this experimental model.
Plasma β-Thromboglobulin in Diabetes Mellitus
Authors: Campbell I W , Dawes J , Fraser D M , Pepper D S , Clarke B F , Duncan L J P , Cash J D
Published: September 2013

The plasma beta-thromboglobulin (βTG) content was measured in 56 diabetic patients with known complications of this disease, including neuropathy, retinopathy, and ischemie skin lesions. Although two patients were found to have elevated levels beyond the normal range, there was no significant difference between the diabetic group as a whole and the group of 35 controls. The significance of these findings with regard to the proposed contribution of small-vessel platelet sequestration in the pathogenesis of late complications of diabetes mellitus is discussed.
Hypoglycemia in Man: Pathologic and Physiologic Variants
Authors: Merimee Thomas J , Tyson John E
Published: September 2013

To determine if an effective method existed for distinguishing the physiologic hypoglycemia of fasting from pathologic hypoglycemia, 72-hour fasts were conducted in 60 women and 20 men of normal weight, in 16 obese subjects, and in six of 11 patients with insulinomas. Only the pattern of change of the immunoreactive-insulin-to-glucose ratio (the I/G ratio), calculated at major time intervals of the fast, provided a clear-cut distinction between these groups; plasma glucose values alone could not make this distinction; The mean fasting I/G ratio was calculated for each subject from that subject's I/G ratios at 12-hour intervals during the fasting period. In no single case did the mean I/G ratio during fasting for an individual of normal weight equal or exceed the control I/G. I/G ratios increased dramatically during fasting in each patient with an insulinoma. Normal obese patients (15 per cent >ideal body weight) did not provide a diagnostic problem, since, regardless of sex, glucose values of less than 55 mg./dl. did not occur. Although the pattern of change of the I/G ratio was extremely useful, the basal I/G ratio alone was potentially misleading; this was due to overlap of basal I/G ratios between subjects with simple obesity and patients with insulinomas. In addition, absolute values for the I/G ratio varied with the technique employed for measuring glucose and insulin. Change of the I/G ratio, however, was independent of the techniques used for measuring glucose and insulin.
Long-term Survival of Adult Rat Islets of Langerhans in Artificial Capillary Culture Units
Authors: Tze Wah Jun , Chen Lydia M
Published: September 2013

Pancreatic islets from adult rats were cultured in artificial capillary culture units that were perfused with nutrient medium. In this in-vitro culture system, islets remain functional for at least 97 days. As determined by insulin radioimmunoassay of the culture medium, islets continue to secrete insulin. Furthermore, islets responded to high glucose concentration in the perifusion medium by increased insulin release throughout the duration of the culture period. A normal appearance of individual epithelioid islet cells and the presence of aldehyde-fuchsin-positive granules were observed in islets fixed in medium. As indicated by the prolonged maintenance of tissue-specific function, the present simple technique for organ culture of intact islets should be useful for providing new information on the long-term effects in vitro of various factors on islet function and a means for the preservation of islets for transplantation.
A Morphologic Study of Intrahepatic Portal-vein Islet Isografts
Authors: Griffith Rogers C , Scharp David W , Hartman Boyd K , Ballinger Walter F , Lacy Paul E
Published: September 2013

Isologous pancreatic islets were implanted into the portal vein of rats with streptozotocin-induced diabetes. At intervals of from one to 32 days after transplantation, the intraheptic islet grafts were examined histologically and ultrastructurally, and their vascular supply was determined by later perfusion studies. Implanted islets were found widely dispersed throughout the liver in peripheral interlobular portal venules and surrounded by vacuolated liver cells containing large stores of glycogen. The endocrine cells were structurally normal in each interval examined. By the third day after transplantation the beta cells were depleted of secretory granules in aldehyde-fuchsin preparations. Regranulation returned by the 14th day and was associated with secretory organelle hypertrophy and hyperplasia. Islet cells were found outside the portal areas in direct apposition to hepatocytes forming distinct desmosomes by the first day. While hemoperfusion of the grafts occurred from the moment of implantation into the portal venule, a ual vascular supply derived from periportal arterial and venous sources developed by the 11th day after transplantation, establishing full vascularization of the grafts. Preliminary work is presented to show that an active ingrowth of nerves in the islet graft occurs in association with the process of vascularization.
Myoinositol Metabolism in Diabetes Mellitus: Effect of Insulin Treatment
Authors: Clements Rex S , Reynertson Richard
Published: September 2013

The metabolism of myoinositol has been studied in 10 nondiabetic subjects and in six patients with diabetes mellitus before and after insulin therapy. While dietary myoinositol intake and fecal myoinositol excretion were similar in both groups, urinary myoinositol excretion was increased 10-fold in the untreated diabetic and accounted for a significant fraction of his dietary myoinositol intake. Insulin treatment restored the urinary myoinositol excretion toward normal. Despite increased myoinositol excretion, plasma myoinositol concentrations were significantly higher in the diabetics following the ingestion of a standard diet or of a 3.0-gm. myoinositol load. This abnormality in oral myoinositol tolerance was also corrected by insulin treatment. The size of the rapidly equilibrating myoinositol pool was significantly decreased in the untreated diabetic and returned to normal following a brief period of insulin treatment.

The elevated plasma myoinositol concentrations observed following myoinositol ingestion in the uncontrolled diabetic presumably represents a combination of enhanced gastrointestinal absorption and impaired intracelhilar transport of myoinositol. The decreased space of distribution of myoinositol also suggests an impairment of intracellular myoinositol transport in the untreated diabetic. These observations are consistent with the speculation that hyperglycemia may condition a widespread relative intracellular myoinositol deficiency in man and suggest that restoration of normal intracellular myoinositol concentrations might prove to be of benefit in the prevention and treatment of certain of the complications associated with human diabetes mellitus.
Carbohydrate Metabolism and Pancreatic Islet-cell Function in Thalassemia Major
Authors: Costin Gertrude , Kogut Maurice D , Hyman Carol , Ortega Jorge A
Published: September 2013

To investigate the development of diabetes mellitus in patients with thalassemia major, plasma glucose and immunoreactive insulin (IRI) levels following oral glucose and intravenous tolbutamide and glucose disappearance rates following intravenous insulin were measured in 10 patients before and during five years on a high transfusion program (HTP). Plasma immunoreactive glucagon (IRG) levels following oral glucose, intravenous insulin, and arginine were measured during the sixth year. Serial percutaneous liver biopsies were performed on seven patients.

The oral glucose tolerance tests (OGTT) and mean peak IRI levels were normal in nine of 10 patients before HTP. After HTP was begun a progressive deterioration of OGTT occurred despite normal IRI levels. Following tolbutamide, the mean per cent fall in plasma glucose in the patients before HTP was significantly less than in controls (p < 0.01) and similar to that of controls during five years of HTP in spite of higher than normal peak IRI levels.

Of seven survivors after six years of HTP, three had normal OGTT and four had chemical diabetes; mean peak IRI levels were normal, but fasting IRG levels were significantly higher than in controls (p < 0.05). In all seven patients, plasma IRG failed to increase following insulin-induced hypoglycemia and was significantly higher than in controls after arginine (p < 0.01); after oral glucose, plasma IRG fell significantly below that of fasting only in the patients with chemical diabetes (p < 0.03). Following intravenous insulin, the mean per cent fall in glucose before and during HTP was significantly less than in controls (p < 0.01). Hemosiderosis and cirrhosis were present in all biopsied patients. Four patients died; two had chemical and two had nonketotic insulin-dependent diabetes.

These data suggest that diabetes mellitus occurs frequently in patients with thalassemia on HTP and that insulin resistance and hyperglucagonemia, possibly due to cirrhosis, are important etiologic factors.
Effect of Ethanol on Stimulus-induced Insulin Secretion and Glucose Tolerance: A Study of Mechanisms
Authors: Shah Jayendra H , Wongsurawat Nirandon , Aran Peter P
Published: September 2013

The effect of ethanol on stimulus-induced insulin secretion was studied, and possible mechanisms were examined in fasting unanes-thetized and unrestrained rats with indwelling jugular and aortic catheters. Glucose (150 mg.) or tolbutamide (10 mg.) was given rapidly, i.v., one hour after a gavage of ethanol or saline (control). Acutely, ethanol treatment caused marked inhibition of glucose-induced insulin secretion and impaired glucose disappearance rate. Tolbutamide-induced insulin secretion was also significantly inhibited, and decline in glucose was significantly less in ethanol-treated rats. In response to ethanol, serum calcium concentration significantly declined for two hours.

In another study, an ethanol metabolite, acetate (0.4 μmole/min.) or vehicle (control) was infused for 60 minutes prior to 150 mg. glucose pulse. Acetate priming significantly potentiated glucose-induced insulin secretion and also improved glucose tolerance.

It is proposed that (1) ethanol in vivo acutely induces hypocalcamie, which inhibits glucose- and tolbutamide-induced insulin secretion—which, in turn, causes glucose intolerance and prevents tolbutamide-induced hypoglycamie. (2) Acetate might be the actual potentiating influence on glucose-induced insulin secretion observed several hours after ethanol treatment.
Glucagon Secretion Induced by Natural and Artificial Amino Acids in the Perfused Rat Pancreas
Authors: Assan Roger , Attali Jean R , Ballerio Giuseppe , Boillot Josette , Girard Jean R
Published: September 2013

The glucagon-secreting potency of 22 amino acids was investigated in the rat isolated perfused pancreas. Arginine and the structurally related amino acids were the most potent A2-cell stimulators that induced a biphasic and sustained glucagon release. Dose-response curves were different for L(+) and D(+)arginine, and the suppressor effect of glucose on the response to L(+) arginine was not detected in the presence of D(+) arginine or homoarginine. Citrul-line was the only exception among the arginine-related amino acids; it displayed neither stimulatory nor inhibitory potency on glucagon release. The A2-cell response to D(+) amino acids and artificial analogues of arginine is a strong case for the theory of amino acid receptors' triggering the release of the hormone before (or in the absence of) further metabolism. The prominent rank of arginine and or ni thine among stimulatory amino acids and some other physiologic evidence suggest that A2-cell may play a regulatory role in the metabolism of ammonia by the liver.
Estimated Life Expectancy of Diabetics
Authors: Bale Gurunanjappa S , Entmacher Paul S
Published: September 2013

Life expectancy among diabetics in Iowa was estimated by using mortality data for the state. The Iowa general population had a higher life expectancy than the diabetic population at every age, except at ages 80 and over for men and ages 75 and over for women. The estimated life expectancy of 59.7 years at birth for diabetic males and of 69.8 years for diabetic females was lower than that for the Iowa general population by 9.1 years among males and 6.7 years among females. This difference narrowed with increasing age. The Iowa figures were similar to the estimates of life expectancy for the diabetic population of Pennsylvania.
A Test of the Hypothesis that the Rate of Fall in Glucose Concentration Triggers Counterregulatory Hormonal Responses in Man
Authors: DeFronzo Ralph A , Andres Reubin , Bledsoe Turner A , Boden Gunther , Faloona Gerald A , Tobin Jordan D
Published: September 2013

The hypothesis that the rate of fall in glucose concentration triggers counterregulatory hormonal responses was tested in five subjects following one hour of sustained hyperglycemie. Despite a rapidly falling blood glucose concentration, no increase in plasma growth hormone, Cortisol, glucagon, or catecholamines occurred as long as the blood glucose concentration remained above fasting levels. Plasma growth hormone, cor tisol, and catecholamines were not released until the mean blood glucose reached 28 mg./100 ml., 39 mg./100 ml., and 39 mg./100 ml., respectively, below the fasting level.

Plasma glucagon was suppressed during the period of hyperglycemia. As the blood glucose concentration fell below basal levels, a progressive increase in glucagon occurred. Plasma glucagon returned to fasting values when the nadir in blood glucose was attained. During the period of rapidly falling blood glucose, only plasma insulin showed any change; its response lagged behind the decline in blood glucose. By the time the fasting glucose level was attained, the plasma insulin was still almost three times the basal level. We concluded that under our experimental conditions the rate of fall in blood glucose and the degree of hypoglycemie achieved is primarily determined by the plasma insulin concentration.
Synthetic Gastric Inhibitory Polypeptide Stimulatory Effect on Insulin and Glucagon Secretion in the Rat
Authors: Taminato Tomohiko , Seino Yutaka , Goto Yasuo , Inoue Yoshimichi , Kadowaki Seizo , Mori Kozaburo , Nozawa Masumi , Yajima Haruaki , Imura Hiroo
Published: September 2013

Effect of synthetic gastric inhibitory polypeptide (GIP) on insulin and glucagon secretion was studied in vivo and in vitro in the rat. Intravenous administration of 1 μg./kg. GIP along with 0.625 gm./kg. glucose caused a more prominent rise of plasma insulin than did 0.625 gm./kg. glucose alone. The suppression of plasma glucagon levels induced by glucose was attenuated partially but not significantly by the concomitant administration of GIP. GIP (1 μg./kg. i.v.) alone raised both plasma insulin and glucagon levels. In in-vi tro experiments with isolated pancreatic islets, GIP significantly augmented insulin release induced by either 8.3 mM or 16.7 mM glucose, whereas the augmentation of glucagon release was observed at 3.3 mM, 8.3 mM, and 16.7 mM glucose concentrations. Three peptides, consisting of 1–28, 22–43, and 15–43 ammo acids of GIP, failed to potentiate insulin and glucagon secretion. These results suggest that synthetic GIP has a stimulating effect on insulin and glucagon secretion.
Potentiation of the Hepatic Action of Insulin by Chlorpropamide
Authors: Blumenthal Stanley A
Published: September 2013

In perfused livers of fed rats, chlorpropamide inhibits glucagon-stimulated glucose production by augmenting the action of insulin. This effect is associated with a decrease in cyclic AMP accumulation in liver and perfusate.

Alterations in glucose production appear to correlate more closely with changes in the amount of cyclic AMP in the perfusate than with changes in intrahepatic concentration of nucleotide.

Potentiation by chlorpropamide of the hepatic action of insulin does not require administration of the drug prior to perfusion. Further, it is demonstrable at concentrations of insulin and glucagon (10−11M) that approximate the normal plasma levels of these hormones.
Effects of Fasting on Insulin Secretion, Islet Glucose Metabolism, and the Cyclic Adenosine 3',5'-Monophosphate Content of Rat Pancreatic Islets In Vitro
Authors: Wolters Gerrit H J , Konijnendijk Willem , Bouman Paul R
Published: September 2013

Fasting for 24 hours inhibits glucose-induced insulin secretion from isolated rat pancreatic islets. At glucose 15 raM the inhibition is only present during the initial 30-45 minutes of stimulation. It decreases at higher glucose concentrations and disappears at glucose 37.5 mM.

In islets of fed rats, 15 minutes of stimulation with glucose 15 mM induced an almost threefold rise of islet cyclic adenosine 3',5'-monophosphate (cAMP). Both this effect and the secretory response were inhibited by about 65 per cent after 24 hours of fasting and almost completely by 72 hours of food deprivation. Fasting for 24 hours also caused a 56 per cent inhibition of the rise of islet cAMP and insulin secretion induced by D-glyceraldehyde 10 mM, but the inhibition was not further enhanced by 72 hours of fasting. Fasting for 24 and 72 hours did not significantly inhibit the islet cAMP response to 15 minutes of stimulation with glucose 37.5 mM.

Fasting for 24 hours impaired neither islet glucose oxidation (14CO2 production) nor over-all glucose utilization (production of 3H-water from [5-3H] glucose) during the initial 30 minutes of stimulation with glucose. After 72 hours of fasting, both over-all glucose utilization and glucose oxidation were reduced by 25 per cent.

These findings suggest that inhibition of the islet cAMP response is a primary factor in the early (24 hours) fasting-induced impairment of the insulin secretory response to glucose stimulation at 5-15 mM. Inhibition of islet glucose metabolism seems to be an independent additional phenomenon that becomes manifest after longer periods of food deprivation.
HLA System in Japanese Patients with Diabetes Mellitus
Authors: Kawa A , Nakazawa M , Sakaguchi S , Nakamura S , Kono Y , Hazeki H , Kanehisa T
Published: September 2013

Seventy-eight Japanese diabetics were HLA-typed, with special reference to age at onset, insulin dependency, and family history.

HLA-A9, B5, and BW40 were increased, but Al, A3, and B8, which are found frequently among Caucasians, were almost absent among Japanese healthy controls as well as diabetics.

J-l, a Japanese specific subclass of BW22, was significantly increased in juvenile-onset diabetics as compared with controls or diabetics with late onset. J-l was also increased in the diabetics with insulin dependency and/or positive family history. But the association of J-l with juvenile-onset diabetes mellitus was found to be the strongest. A tendency to a decrease in B5 was also observed in Japanese diabetics with juvenile onset, but this did not reach statistical significance as far as corrected P was concerned. These results showed that genetic markers for diabetes mellitus, especially that with juvenile onset, were different among Japanese from those found among Caucasians.

There is ample evidence to indicate a race specificity in HLA phenotypes in diabetics as well as in controls.

These findings also strongly suggest that juvenile-onset diabetes mellitus is a disease entity in itself and different from late-onset diabetes mellitus in origin and pathogenesis.
C-peptide Response to Glucagon: A Test for the Residual β-cell Function in Diabetes Mellitus
Authors: Faber O K , Binder C
Published: September 2013

Pancreatic β-cell secretory activity was measured in 17 patients with insulin-dependent diabetes mellitus of less than 19 months' duration and in 10 nondiabetic subjects by means of the peripheral plasma C-peptide response to 1 mg. of glucagon i.V. The C-peptide response to a meal was also measured in the diabetic patients.

Residual β-cell function was present in all the diabetic patients as indicated by significant amounts of C-peptide in plasma. Significant increases in C-peptide were observed in 16 after glucagon stimulation and in 15 after the meal. Both absolute and relative increase in C-peptide were reduced in the diabetic patients. The increase in C-peptide was correlated to the fasting C-peptide concentration both after glucagon (r = 0.86, p < 0.001) and after the meal(r = 0.66, p < 0.01). The responses to the meal and to glucagon were correlated (r = 0.77, p <0.005), indicating a high predictive value of the glucagon test as to how the β-cells will respond during normal daily life.
Nesidioblastosis: The Pathologic Basis of Persistent Hyperinsulinemic Hypoglycemia in Infants: Morphologic and Quantitative Analysis of Seven Cases Based on Specific Immunostaining and Electron Microscopy
Authors: Heitz Philipp U , Klöppel Günter , Häcki Walter H , Polak Julia M , Pearse A G Everson
Published: September 2013

Seven surgical specimens of pancreas, obtained at laparotomy from infants suffering from persistent hyperinsulinemic hypoglycemia, were analyzed by qualitative and quantitative immunocytochemistry and by electron microscopy. In five cases a multifocal ductuloinsular proliferation, in one a focal adenomatosis, and in one a solitary encapsulated nodule (adenoma) were observed. Combinations of the different patterns of proliferation were seen in six cases. Budding off from the ductular epithelium and interposition of endocrine cells between ductular epithelial cells were prominent features common to all cases. An almost fivefold increase of the mean total area occupied by endocrine tissue was found over that of age-matched controls. Four cell types were seen to participate regularly in the proliferation, and their ratios were remarkably constant in all cases, mean figures being 62:21:9:8 per cent for B:A:D:D1 cells, respectively. The ratio of B cells per total endocrine area in nesidioblastosis was very close to that per islet of the controls (62:59 per cent).

Since common features were found in all or in the majority of cases, it is suggested that the various patterns of proliferation are merely morphologic variations of the same basic defect. Nesidioblastosis may result from inappropriately controlled development of the endocrine pancreas that is not arrested but carries on beyond birth and during infancy. The application of specific immunocytochemistry as a necessity for full appreciation of the extent of endocrine proliferation is stressed.