bluuebunny/crossref_metadata_2025_split huggingface dataset:
Responses of Patients with Insulinomas to Stimulators and Inhibitors of Insulin Release That Have Been Linked with Cyclic Adenosine Monophosphate
Authors: Lins Per-Eric , Efendić Suad 
Published: September 2013

The study comprises nine consecutive patients who had pancreatic beta-cell tumors and spontaneous hypoglycemia, seven of whom had verified, benign insulinomas and one a malignant insulinoma with metastases to the liver. The ninth patient, who refused surgery, was followed for three years without displaying any signs of malignancy. Among the patients with benign insulinomas, three showed exaggerated, two normal, and two unusual insulin responses to glucose. One such patient as well as the one with a malignant tumor did not respond to glucose. In general, the insulin responses to glucagon were similar to those to glucose. Somatostatin reduced basal insulin levels as well as the responses to glucose and glucagon only in subjects with normal or exaggerated responses to these agents. Einephrine behaved like somatostatin when insulin release was stimulated by glucose, but it was a weak inhibitor of the glucagon-stimulated response. The subject with the malignant insulinoma did not respond to either glucose or somatostatin. The remission of the disease, which followed streptozotocin treatment, was accompanied by restoration of the normal responsiveness to the above agents.
Glucagon stimulates insulin release by increasing the intracellular level of cyclic adenosine monophosphate (AMP). The effects of glucose, somatostatin, and epinephrine are supposed to be mediated, at least partially, by way of the adenylcyclase-cyclic AMP system. Therefore, the present data suggest that the variability of the beta-cell responsiveness to glucose and glucagon in patients with insulinoma reflects the responsiveness of the adenylcyclase-cyclic AMP system of the beta-cell tumor, which may be exaggerated, normal, or absent.
Effect of Fasting on the Release of Insulin and Somatostatin from Perifused Islets of Langerhans
Authors: Schauder Peter , McIntosh Christopher , Arends Jann , Frerichs Heiko 
Published: September 2013

Release of somatostatin and insulin from perifused islets of fasted and control rats was compared. After a fasting period of 48 h glucose-induced insulin release but not somatostatin release was diminished. Islets from fasted rats released significantly more somatostatin in the presence of 3.3 mM glucose than islets from controls. Simultaneously, the somatostatin content of isolated islets from fasting rats was significantly decreased.
The results indicate that the low secretory activity of islet B cells in the fasting state is associated with a high secretory activity of islet D cells.
Localization of Occult Insulinoma by Super-Selective Pancreatic Venous Sampling for Insulin Assay through Percutaneous Transhepatic Catheterization
Authors: Millan Victor G , Urosa Claudio L , Molitch Mark E , Miller Harry , Jackson Ivor M D 
Published: September 2013

Preoperative localization of insulinomas by arteriography is successful only 66% of the time. With small tumors, intraoperative localization is usually unsuccessful also. Because surgical morbidity and mortality are increased greatly when major, blind, pancreatic resections or reoperations are performed, additional preoperative localization procedures are needed. We now report the successful localization of an occult insulinoma by means of blood sampling for insulin radioimmunoassay, obtained by selective pancreatic vein sampling through percutaneous transhepatic catheterization.
Our patient had symptoms of fasting hypoglycemia for 11 months. Routine studies were normal and two fasting plasma glucose concentrations were 34 and 16 mg/dl to correspond with insulin values of 33 and 75 μU/ml. Celiac arteriography was normal. Percutaneous transhepatic portal and pancreatic venous catheterization revealed insulin concentrations (μU/ml) of between 23 and 36 in portal and splenic veins, 17 in the short, gastric vein, 17 in the dorsal pancreatic vein, 19 in the superior, mesenteric vein, and 61 and 288 in two pancreatic magna veins draining the tail. An insulinoma of 2 × 3 cm was resected from the tail. On the basis of our experience with this patient, it is clear that selective venous sampling may facilitate the localization of occult insulinomas at surgery and thereby avoid extensive, blind, pancreatic resections and the need for reoperation.
Characteristics of Growth Hormone Secretion in Clinically Stable Diabetes
Authors: Merimee Thomas J , Fitzgerald Constance R , Gold Larry A , McCourt Jerome P 
Published: September 2013

Although the secretion of growth hormone (GH) is widely accepted as being increased in diabetes mellitus, this conclusion appeared to us to be the result of bias in case selection. Newly diagnosed and hospitalized diabetics cannot be assumed as representative of the clinically stable diabetic state. In view of the postulated importance of growth hormone to the vascular complications of diabetes, we re-examined this problem in 58 clinically stable diabetics and 38 age-matched controls. GH was measured in serum samples collected hourly during a 24-h period of normal activity.
Control and clinically stable diabetic subjects of normal weight had similar mean serum GH concentrations for 24 h. In subjects of normal weight, values were 4.4 ± 0.6 ng/ml for women of the control group and 4.0 ± 0.8 ng/ml for diabetic women (P = NS) and values in men were 2.4 ± 0.3 ng/ml in controls and 2.1 ± 0.3 ng/ml in diabetic men (P = NS). Obese controls and obese diabetics had similar, but significantly lower values than nonobese subjects.
When hyperglycemia (125 mg to 175 mg/dl) was induced in 12 control subjects for 24 h, glycemia was obtained comparable to that seen in a select group of nine diabetics. Mean serum concentrations of GH were significantly less in the glucose-infused controls than in both euglycemic controls and diabetics.
These data do not support an absolute increase of circulating GH in stable diabetics; GH levels appear to be normal in this group but inappropriate for the level Of glycemia.
Severe Hyperglycemia: Effects of Rehydration on Endocrine Derangements and Blood Glucose Concentration
Authors: Waldhäusl W , Kleinberger G , Korn A , Dudczak R , Bratusch-Marrain P , Nowotny P 
Published: September 2013

Diabetic ketoacidosis is associated with an excess secretion of counterregulatory hormones. The effect of rehydration on these endocrine derangements before insulin administration is unknown. Therefore, we measured the effect of rehydration with hypoosmolal fluid (220 mosmol/kg) on blood glucose (BG), immunoreactive insulin (IRI), immunoreactive C-peptide (IRCP), immunoreactive glucagon (IRG), human pancreatic polypeptide (hPP), growth hormone (GH), prolactin (PRL), cortisol, aldosterone, renin (PRC), epinephrine, norepinepnrine, and parathyroid hormone (PTH) in ketoacidotic diabetic patients [pH 7.03 ± 0.05 (SEM); n = 8] and in patients (n = 2) with nonketotic hyperglycemia (BG, 29.8 mmol/L and 46.8 mmol/L). The cumulative net fluid balance after rehydration was 4364 ± 690 ml. Basal insulin was inappropriately low, and IRCP was below the normal range (1.5 ± 0.5 ng/ml). Serum osmolality fell during hypoosmolal rehydration (n = 9) from 335 ± 11 to 315 ± 9 mosmol/kg. Rehydration with hypoosmolal fluid with bicarbonate added at a pH of less than 7.2 induced a fall in BG ranging from 6.1 mmol/L to 22.6 mmol/L, or of 16.7% to 79.8% of the initial BG level, as well as a decrease in plasma lactate and urinary glucose. These effects were paralleled by a decrease in IRG, cortisol, epinephrine, norepinephrine, aldosterone, and PRC. No fall in BG was seen in one patient whose dehydrated state was maintained by infusion of isotonic saline. Low dose insulin treatment was initiated in all patients immediately when no further fall in blood glucose levels was achieved.
We conclude that rehydration improves the metabolic situation in severe diabetic hyperglycemia and ketoacidosis by reducing (a) the availability of counterregulatory hormones and (b) peripheral insulin resistance on a cellular level. Thus, proper rehydration will support the beneficial action of simultaneous low dose insulin treatment in patients with severe hyperglycemia.
Insulin Resistance Caused by Massive Degradation of Subcutaneous Insulin
Authors: Paulsen Elsa P , Courtney John W , Duckworth William C 
Published: September 2013

Severe resistance to subcutaneous insulin but sensitivity to intravenous insulin persisted for 15 months in a 17-year-old diabetic girl. Heat-labile insulin-degrading activity was present in the patient's ketotic sera and in the 100,000 g fraction (soluble fraction) of adipose tissue. Serum-degrading activity was not inhibited by N-ethylmaleimide. The soluble fraction also degraded glucagon and B chain but not growth hormone or myoglobin. It was inhibited by incubation with the patient's nonketotic sera, normal sera, or Trasylol. Glutathione-insulintranshydrogenase (GIT) activity was 66% of normal.
The biopsy of adipose tissue at remission showed a normal level of insulin- and glucagon-degrading activity. The activity was eluted from Sephadex G200 as a single peak and had properties consistent with those of the insulin-specific protease (ISP).
The increased degrading activity present during insulin resistance had properties not shared with ISP, suggesting the presence of an uncharacterized protease.
Cellular Mechanisms of Insulin Release: Effects of Retinol on Insulin Release and Islet Ultrastructure
Authors: Chertow Bruce S , Buschmann Robert J , Kaplan Robert L 
Published: September 2013

In previous studies using perifused collagenase-isolated rat islets, retinol (vit A) inhibited glucose-induced Diphasic insulin release and glucose oxidation. To further evaluate vit A action and elucidate cellular mechanisms of insulin release, we tested the effects of vit A on glucose uptake by islets, on other stimuli of insulin release, and oh islet ultrastructure and the effects of calcium on vit A inhibition of insulin release. Vit A did hot inhibit 2-deoxy-D-glucose uptake into islets. Vit A inhibited second phase 9.7 and 13.9 mM glucoseinduced insulin release to 50%, 10 mM glyceraldehydeinduced release to 64%, and 20 mM leucine-induced release to 66% of control. First phase, release was unaffected. Kinetic analysis of the effects of vit A on glucose-induced release indicated a change in the Vmax but not in the Km, suggesting inhibition of a potentiator of insulin release by vit A. Calcium (4 mM) opposed vit A inhibition of glucose-induced release.
Ultrastructurally, vit A decreased the volume fraction of secretory granules to 90% of control, increased the volume fraction of material within the rough endoplasmic reticulum to 147% of control, and increased the outer and decreased the inner mitochondrial compartment volume fractions by 14%.
Our functional and ultrastructural findings, in all, suggest that vit A inhibitioh of second phase insulin release is not specific for glucose and may be mediated in part through impairment of mitochondrial function and intracellular glucose oxidation.
The Correlation of Arteriosclerosis Obliterans with Lipoproteins in Insulin-Dependent and Non-Insulin-Dependent Diabetes
Authors: Beach Kirk W , Brunzell John D , Conquest Loveday L , Eugene Strandness D 
Published: September 2013

Risk factors for arteriosclerosis, such as age, duration of diabetes, sex, and plasma lipoprotein levels, were correlated with the presence of arteriosclerosis obliterans (ASO) as determined by noninvasive methods in 485 of 506 subjects studied with diabetes mellitus.
The diabetic subjects were separated into two major groups for analysis: insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM). The NIDDM group was subdivided into those treated by diet (NIDDM-D), sulfonylureas (NIDDM-S), and insulin (NIDDM-I).
Overall, lipoprotein levels in the diabetics were higher than in an age- and sex-adjusted nondiabetic group. Cholesterol levels were elevated in all females and HDL cholesterol levels were depressed in diet- and sulfonylurea-treated females. VLDL levels were most elevated in diet-treated subjects followed by sulfonylurea-treated subjects; VLDL levels in insulin-treated subjects were not elevated.
The prevalence of ASO is related to different factors in each group. In IDDM and NIDDM-I subjects, VLDL triglyceride, LDL cholesterol, and duration of diabetes or age are important risk indicators. By contrast, in NIDDM-S subjects, age alone is the significant risk indicator, and in NIDDM-D subjects, inverse HDL cholesterol correlated with ASO. While males have a higher prevalence of ASO than females, the difference is not statistically significant in any group. Other possible factors, such as hypertension, smoking, and obesity, were not considered in this initial analysis.
Metabolic Effects of Sodium Dichloroacetate in Normal and Diabetic Dogs
Authors: Ribes Gérard , Valette Guy , Loubatières-Mariani Marie-Madeleine 
Published: September 2013

The effects of acute and chronic administration of sodium dichloroacetate (DCA) were studied in the normal and diabetic dog. In the normal dog, a single oral injection of DCA (150 mg/kg) provoked a rapid decrease of the lactate, pyruvate, and triglyceride concentrations and a progressive decrease of blood glucose. These effects lasted longer than 24 h.
In the alloxan-diabetic dog deprived of insulin for 72 h, DCA induced a decrease of blood glucose, lactate, and pyruvate concentrations as well as of glucosuria. In these ketotic animals, the plasma lipid compounds and the blood and urinary ketone bodies were not significantly changed by DCA.
In the normal dog, the chronic administration of DCA (150 mg/kg daily for 7 days) provoked a decrease in blood glucose, lactate, pyruvate, and oxaloacetate concentrations, which returned to starting values only within 2 to 5 days after the end of the treatment, depending on the compounds studied. A decrease of cholesterol was also noted. During the chronic administration of DCA, blood β-hydroxybutyrate and acetoacetate concentrations strongly increased.
When treated with insulin alone, the alloxan-diabetic dogs had a high blood glucose concentration; the blood lactate, pyruvate, and oxaloacetate concentrations did not differ significantly from those of the normal animals, however. In these diabetic dogs, the lipid compounds and, particularly, the ketone compounds were increased. The addition of DCA (75 mg/kg daily for 7 days) provoked a drop in blood lactate, pyruvate, and oxaloacetate levels, and a reduction of blood glucose and plasma cholesterol, triglyceride, and total lipids was also noted. Blood β-hydroxybutyrate and acetoacetate concentrations, which were already high at the start, were not affected when DCA was associated to insulin. This addition of DCA provoked a rapid and marked reduction in glucosuria, which was concomitant with an increase in urinary β-hydroxybutyrate and acetone.
The Glucose Intolerance of Acute Pancreatitis: Hormonal Response to Arginine
Authors: Solomon Solomon S , Duckworth William C , Jallepalli Panduranga , Bobal Mary Alice , Iyer Ramamurthi 
Published: September 2013

Patients with acute pancreatitis were studied by arginine infusion at 48–72 h, 7–10 days, and 18–21 days after onset of their illness. Plasma glucose, insulin, and glucagon values were determined. Acute pancreatitis was characterized by fasting hyperglycemia and hyperglucagonemia, associated with relative hypoinsulinemia. Arginine stimulation early in the disease (48–72 h) demonstrated hyperglycemia and hyperglucagonemia, which normalized by 18–21 days. Both phases of the normal biphasic insulin response to arginine were decreased during the initial arginine infusion. By 18–21 days, although the first phase was completely normal, the second phase of insulin secretion remained depressed.
Acute pancreatitis is associated with damage to both the endocrine and exocrine pancreas. Glucose intolerance seen with this disease appears to be the result of hyperglucagonemia and relative hypoinsulinemia. Although the healing process at 3 wk is associated with return of plasma glucose and glucagon concentrations to normal, the impaired second phase insulin secretion persists.
Red Cell Sorbitol: An Indicator of Diabetic Control
Authors: Malone John I , Knox Gail , Benford Stephen , Tedesco Thomas A 
Published: September 2013

SUMMARY
Intact human erythrocytes accumulate intracellular sorbitol in response to the medium's glucose concentration during in vitro incubations. Sorbitol was identified and measured both enzymatically and by gas-liquid chromatography. The sorbitol produced is most likely a result of the activity of aldose reductase, since (1) a low glucose concentration in the medium elicits this response, and (2) this activity is completely blocked by tetramethylene glutaric acid, a specific inhibitor of aldose reductase. Erythrocyte sorbitol levels in insulin-dependent diabetics are clearly above those of nondiabetics after an 8 h fast. A good correlation exists between red cell sorbitol content and coincident plasma glucose concentrations. Individual exceptions to this rule exist, however, and suggest that red cell sorbitol levels may provide information about in vivo polyol pathway activity that may be important in the pathogenesis of diabetes-associated complications.
Epinephrine-induced Hypoaminoacidemia in Normal and Diabetic Human Subjects: Effect of Beta Blockade
Authors: Shamoon Harry , Jacob Ralph , Sherwin Robert S 
Published: September 2013

SUMMARY
To evaluate the effect of epinephrine on the circulating amino acids, we infused epinephrine into normal human subjects and juvenile-onset diabetic patients given a constant basal infusion of insulin. Epinephrine infusion produced an identical 350–400 pg/ml rise in plasma epinephrine in both groups. In normal subjects, epinephrine caused a progressive 26% reduction in total circulating amino acids, despite unchanged levels of plasma insulin. This effect was most pronounced for the branched amino acids, which fell by 40% (P &lt; 0.001). Plasma alanine was the only amino acid which failed to decline. Similarly, infusion of epinephrine in the insulin-infused diabetics produced a 23% fall in total amino acids, a 37% decline in branched chain amino acids, but no change in plasma alanine. Saline infusion in the insulin-infused diabetics had no effect on plasma amino acid concentrations. In addition, when epinephrine was infused into two insulin- withdrawn diabetics, a comparable hypoaminoacidemic response was observed. The infusion of propranolol in both normal and diabetic subjects totally prevented the epinephrine-induced fall in plasma amino acids.
It is concluded that (1) increments in epinephrine similar to those observed in stress cause a decline in circulating amino acids (except alanine) which is greatest for the branched chain amino acids; (2) this hypoaminoacidemic effect occurs in the absence of a rise in plasma insulin and diabetic subjects, as well; and (3) epinephrine-induced changes in amino acid regulation are prevented by β-adrenergic blockade. Our findings suggest that, in contrast with glucose and fat metabolism, epinephrine and insulin may have similar, rather than antagonistic, effects on plasma amino acid metabolism.
Arteriosclerosis Obliterans and Associated Risk Factors in Insulin-dependent and Non-insulin-dependent Diabetes
Authors: Beach Kirk W , Strandness D Eugene 
Published: September 2013

SUMMARY
The prevalence of arteriosclerosis obliterans (ASO) of the legs was determined by a battery of noninvasive tests in 141 insulin-dependent and 289 non-insulin-dependent diabetic subjects and in 64 other subjects. The prevalence of detectable ASO ranges from 18% in the younger IDDM group to 41% in the diet-treated NIDDM group.
The prevalence of ASO increases 7.5% per decade, appears to increase 6.5% in the age-adjusted IDDM group, 9% in males, 19% in those with hypertension, and 12% in smokers. No consistently significant correlations with fasting glucose, glycosylated hemoglobin, or obesity were found. After accounting for the effect of smoking, the increased risk for ASO in males becomes nonsignificant.
Hypersecretion of Pancreatic Somatostatin in the Obese Zucker Rat: Effects of Food Restriction and Age
Authors: Trimble Elisabeth R , Herberg Lieselotte , Renold Albert E 
Published: September 2013

SUMMARY
Islets of 5-mo-old obese Zucker rats secreted 50% more somatostatin (SRIF) in response to 8.3 mM or 16.7 mM glucose than did islets from lean controls; the islet SRIF contents of obese and lean rats were similar. As expected, islets of obese rats demonstrated a greater basal and a fivefold greater glucose-induced insulin release and also a twofold greater insulin content than did islets from lean rats. Obese rats were pair fed with lean animals from the age of 9 wk until killed, when 5 mo old. While this curtailed the weight gain of obese rats to that of lean controls, it caused no reduction in the per cent body weight found in the form of lipid. The responses of the pancreatic delta and beta cells to pair feeding were markedly different. Pair feeding caused no alteration in either SRIF content or glucose-induced SRIF release, while the expected reductions in both islet insulin content and glucose-induced insulin secretion were observed.
Islets from older obese Zucker rats (15–18 mo old) had four to five times greater contents of both SRIF and insulin than did islets from age-matched lean controls. The obese rats of this age had a moderate glucose intolerance. SRIF secretion from the islets of such rats was distinctly greater than from those of lean controls at all glucose concentrations tested (range, 1.0–16.7 mM). The delta cells of the older obese rats had lost their sensitivity to glucose, while those of lean controls remained sensitive. Beta cells of islets from both obese and lean 15-mo-old rats remained glucose sensitive. Under all conditions tested, secretion of SRIF and insulin was greater from islets of obese than lean rats.
The results demonstrate a marked difference in pancreatic delta and beta cell responses to pair feeding in the obese Zucker rat. At present, the roleplayed by hypersecretion of pancreatic SRIF in the obesity syndrome of the Zucker rat remains obscure.