bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kinetics of Native Insulin in Diabetic, Obese, and Aged Men
Authors: McGuire Elizabeth Ann , Tobin Jordan D , Berman Mones , Andres Reubin 
Published: September 2013

The kinetics of unlabeled porcine insulin were studied in 69 nondiabetic male subjects aged 18–83 yr with obesity indexes of 0.93–1.51 and in 12 maturity-onset diabetics age 46–78 yr with obesity indexes of 0.95–1.56 by using the euglycemic clamp technique. Analysis of the insulin kinetic data by using a mathematical model permitted the determination, for each individual, of steady state distribution masses and degradation rate constants. The individuals were grouped to allow comparison of the results on the basis of age, obesity index, or diabetes. The responses over a period of 120 mm to an infusion and wash out of insulin show some transient as well as steady state differences with age, obesity, or diabetes. Analysis of these data by use of compartmental models leads to the conclusion that in the steady state the ratio of insulin in extravascular spaces to that in plasma (T/P) is decreased in the moderately obese group (26%) and in the diabetic group (17%) but increased in the older group (13%) when each is compared with the appropriate control. Since extravascular insulin includes both insulin bound to receptors and insulin in the interstitial fluid, the observed changes in the extravascular to plasma mass ratio most likely reflect changes in in vivo binding to receptors, although the magnitude of the change would be modified somewhat by changes in the size of the interstitial spaces relative to plasma. In addition, the rate of entry of new insulin into plasma (BSDR) was increased in the diabetic population (45%; P &lt;0.02) as well as in the moderately obese group (27%) but was decreased somewhat in the older group (11%).
The following general conclusions can be drawn from the results: The pattern of parameter changes seen with obesity is similar to that seen with maturity-onset diabetes. The decrease in T/P seen with obesity and with maturity-onset diabetes cannot be accounted for solely by changes in fasting plasma insulin levels in these populations. The pattern of changes seen in the older subjects is opposite that seen in the maturity-onset diabetics, which suggests that diabetes is a perturbation distinct from the normal aging process. Finally, the changes in the metabolism of insulin are not large, making it unlikely that they are the sole cause of the major alterations in glucose tolerance seen with aging, obesity, or diabetes.
Influence of Arginine on Splanchnic Glucose Metabolism in Man
Authors: Bratusch-Marrain P , Björkman O , Hagenfeldt L , Waldhäusl W , Wahren J 
Published: September 2013

To examine the mechanism of the arginine-induced rise in blood glucose concentration, splanchnic glucose output (SGO) and precursor uptake were studied during i.v. infusion of arginine (30 g/30 min) with and without somatostatin infusion (500 μg/h, 90 min) in postabsorptive and in 60-h fasted healthy subjects. The hepatic venous catheter technique was employed.
In the postabsorptive state, arginine infusion was accompanied by an eightfold and a fivefold increment, respectively, in the hepatic venous concentration of insulin and glucagon; SGO doubled and blood glucose increased by 30%. After cessation of arginine infusion, SGO and blood glucose returned to basal levels within 30 min.
When both arginine and somatostatin were administered, glucagon rose threefold, whereas the insulin response was abolished. And while the rise in SGO during arginine infusion and its subsequent decline were uninfluenced by the simultaneous infusion of somatostatin, the rise in blood glucose was more pronounced and the glucose concentration remained elevated longer than in control studies without somatostatin. Splanchnic uptake of glucogenic precursors was uninfluenced by arginine infusion, with or without simultaneous somatostatin administration.
In the 60-h fasted group, arginine infusion was accompanied by a minimal increase in insulin but a fivefold elevation of the glucagon level. Combined arginine and somatostatin infusion did not boost insulin significantly but the glucagon level rose threefold above the basal value. Basal SGO was 55% lower than in the postabsorptive state, and it rose in response to arginine administration (+50%) as well as during combined arginine and somatostatin infusion (+80%). No significant change in splanchnic uptake of glucogenic precursors was observed during arginine infusion with or without somatostatin administration.
We conclude that (1) arginine infusion is accompanied by a rise in SGO and blood glucose due to arginine-induced stimulation of glucagon secretion, (2) the rise in SGO is caused primarily by glucagon-stimulated hepatic glycogenolysis, and (3) combined somatostatin and arginine administration is accompanied by a more marked rise in blood glucose due to hypoinsulinemia and reduced peripheral glucose Utilization.
Syngeneic Transplantation of Fetal Rat Pancreas: III. Effect of Insulin Treatment on the Growth and Differentiation of the Pancreatic Implants After Reversal of Diabetes
Authors: McEvoy Robert C , Hegre Orion D 
Published: September 2013

Eight 18-day fetal pancreases were transplanted to syngeneic alloxan diabetic male rats. Some of the recipients were treated with insulin for a 7-day period immediately after transplant. By previously published clinical criteria, three groups of recipients could be identified after reversal of diabetes by the transplanted tissue: insulin-treated rapid reversal; insulin-treated slow reversal; and control (not treated with insulin). Five animals in each group were sacrificed after glucose tolerance testing for morphologic and hormonal analysis of the transplanted tissue. The insulin-, glucagon-, and somatostatin-positive islet cell masses of the fetal pancreatic implants were quantitated.
There was a correlation between the beta cell mass of of the implants and the glucose tolerance exhibited by the host animals. The rapid response insulin-treated recipients had significantly greater implant beta cell mass and insulin content compared with the other groups. There was no difference in implant alpha cell mass among the groups, but the insulin-treated implants had a significantly greater glucagon content. The delta cell mass of insulin-treated rapid response was less than that of the other two groups.
The results are discussed in relation to previously reported morphometric analysis 15 days after transplantation. The relationships of transplanted beta cell mass, beta cell differentiation, transplant site, and cell-to-cell interactions within the transplanted islet to the control of glucose homeostasis are also discussed.
Control of Gastric Glucagon Secretion in the Acutely Pancreatectomized Rat
Authors: Marre M , Bobbioni E , Suarez M , Reach G , Dubois M P , Assan R 
Published: September 2013

Glucagon immunoreactivity (IRG) was measured in portal plasma from control and pancreatectomized rats and in arterial plasma from eviscerated rats with a functional liver. Portal IRG was 0.41 ± 0.02 ng/ml in control rats and 0.22 ± 0.01 in pancreatectomized rats. After evisceration, values of 0.08 ± 0.01 ng/ml were found (unextracted plasma, antiserum 30 K). Acid-ethanol plasma extracts demonstrated lower values, but a similar stepwise decrease was observed after pancreatectomy, then gastrectomy. Rat gastric extracts contained a low concentration of IRG (approximately 1/1200 the C-terminal IRG concentration of the corresponding pancreas). No IRG-positive cells were detected by immunofluorescence in the gastric mucosa.
In the pancreatectomized rats, portal IRG remained stable for 75 min in the absence of further manipulation. From IRG concentrations and hepatic blood flow estimation in both control and pancreatectomized rats, the contribution of the stomach to portal IRG in the basal state could be estimated as 20% of the total. Gastric IRG release was increased by acute hypoglycemia (peak value 0.75 ± 0.18 ng/ml; N = 10; P &lt; 0.01) and by 2-deoxyglucose infusion (0.45 ± 0.15 ng/ml; N = 4; P &lt; 0.05). Administration of glucose + insulin induced a decrease in portal IRG (0.13 ± 0.01 ng/ml; N = 4; P &lt; 0.001). Vagal stimulation and arginine infusion induced a rise in portal IRG: 0.84 ± 0.27 ng/ml (N = 10; P &lt; 0.05) and 0.31 ± 0.03 ng/ml (N = 9; P &lt; 0.01), respectively, while portal insulin remained low or undetectable (0-18 μu/ml). A rise in blood glucose accompanied the increase of plasma IRG. A concomitant insulin-induced hypoglycemia (36 ± 5 mg/dl) strongly potentiated the effects of both arginine infusion (1.46 ± 0.47 ng/ml; N = 6; P / 0.005) and vagal stimulation (1.39 ± 0.47 ng/ml; N = 4; P &lt; 0.005).Higher IRG values were observed after pancreatectomy in alloxan-diabetic rats: 0.36 ± 0.02 ng/ml (N = 3; P &lt; 0.001).
We conclude therefore that: (a) the rat stomach contributes to the release of IRG in blood but to a limited extent, (b) the factors controlling this release appear very similar to those controlling pancreatic A cells; and (c) gastric IRG may be hyperglycemic in the rat.
Factors Related to Diabetes Mellitus in Puerto Rican Men
Authors: Cruz-Vidal Mercedes , Costas Raúl , García-Palmieri Mario R , Sorlie Paul D , Hertzmark Ellen 
Published: September 2013

Urban-rural comparisons of the prevalence of diabetes were made in a cohort of 2567 rural and 6190 urban participants aged 45 to 64, in the Puerto Rico Heart Health Program. The prevalence of diabetes in the urban population was more than double that in the rural. Consistent with this, blood glucose concentrations were significantly higher in urban than in rural populations.
The prevalence of diabetes increased with age and relative weight. It was associated with elevations of serum cholesterol, blood pressure, and fasting serum triglycerides. A positive family history was found more commonly in diabetics than in nondiabetics. If there was a history in both a sibling and a parent, there was at least a threefold increased prevalence over those with no family history.
The reason for the higher prevalence of diabetes in the urban than in the rural area is elusive. In obese men, the urban and rural prevalence rates are the same, but, among relatively lean men, the prevalence in the urban area is twice that of the rural men.
The Mechanism of Zinc Uptake in Isolated Islets of Langerhans
Authors: Ludvigsen Carl , McDaniel Michael , Lacy Paul E 
Published: September 2013

The uptake of zinc65 (Zn) was determined in isolated pancreatic islets employing a dual isotope procedure with sucrose as an extracellular marker. Islets slowly accumulated Zn over long periods of time (24 h or longer) reaching three to five times the extracellular concentration by 70 min and a 30-fold differential over extracellular concentration by 24 h. Zn uptake at low concentrations (0.5–7 μM) demonstrated saturation kinetics with the Km and Vmax, 1.5 nM and 11.1 Fmol/islet/min, respectively. At higher Zn concentrations (10–3000 μM), a linear relationship between initial rates of uptake and Zn concentration was observed. Zn at a low concentration (2 μM) was countertransported by 2 mM ZnCI2 pretreatment and inhibited by the presence of cadmium (2–20 μM). Countertransportation and cadmium inhibition of Zn uptake was not found at a higher Zn concentration (44 μM). Zn uptake at either 2 or 44 μM was not inhibited by pretreatment and presence of 300 μM dinitrophenol. Lowering of temperature from 37 °C to 20 °C and 4 °C depressed Zn uptake at 44 μM by 65% and 82%, respectively. However, at 2 μM Zn, the uptake was equivalent at 20 °C and 37 °C and showed a decrease of 70% at 4 °C. Zn uptake at either 44 or 2 μM in short (1–70 min) or long (1–24 h) studies was unaffected by concentrations of glucose that stimulated insulin secretion.
The results present the evidence that a facilitated mechanism of Zn transport predominates at low Zn concentrations and a diffusion mechanism of entry predominates at higher Zn concentrations.
Capillary Basal Laminar Thickness in Diabetic Human Myocardium
Authors: Fischer Vernon W , Barner Hendrick B , Leskiw M Lisa 
Published: September 2013

Biopsied myocardial tissue was obtained from 24 patients electing coronary arterial bypass surgery who were divided into three groups: chemical diabetics (CD) with normal fasting blood sugar levels and incidentally encountered elevated glucose levels after sugar loading; overt diabetics (OD) requiring insulin treatment; and euglycemic, nondiabetic patients (ND) serving as a control group. Specimens from the left anterior apical segment of the heart were processed for ultrastructural examination, with special emphasis on determining capillary basal laminar thickness with the aid of morphometric techniques.
Results of this study indicate that (1) a statistically significant increase in basal laminar thickness is evident in myocardial tissue of OD patients; (2) incipient alterations in laminar width are demonstrable in the CD group; (3) the predominant morphologic abnormalities, which we have examined in the parenchymal tissue of the biopsied hearts, namely myocardial hypertrophy and interstitial fibrosis, are present to a comparable degree in all three groups of patients; and (4) the average thickness of basal laminae around myocardial capillaries tends to be narrower compared with measurements reported in other tissue compartments.
Acetylsalicylic Acid Restores Acute Insulin Response Reduced by Furosemide in Man
Authors: Giugliano Dario , Torella Roberto , Sgambato Saverio , D'Onofrio Felice 
Published: September 2013

Prostaglandin E (PGE) infusion in normal man inhibits the acute insulin response to glucose. In order to determine whether endogenously released PGE might also inhibit insulin secretion, glucose-stimulated insulin responses were investigated in normal volunteers after furosemide (40 mg i.v.), a stimulator of endogenous PGE synthesis. Acute insulin response to glucose (20 g i.v.) was significantly reduced by furosemide (response before furosemide: 36 ± 5 μU/ml; after furosemide: 26 ± 5 μU/ml, m ± SE, mean change 3−10 min, N = 8, P &lt; 0.01), whereas glucose disappearance rates were not modified after furosemide, Infusion of lysine acetylsalicylate (LAS), ah inhibitor of endogenous PGE synthesis, completely reversed the inhibitory effect of furosemide on insulin secretion and also augmented acute insulin response to glucose (response before furosemide + LAS: 41 ± 6 μU/ml; during furosemide + LAS: 50 ± 7 μU/ml, N = 10, P &lt; 0.02). This effect was associated with an increase in glucose disappearance rates (P &lt; 0.05).
These findings demonstrate that (1) furosemide inhibits glucose-induced acute insulin responses and (2) LAS completely reverses the inhibitory effect of furosemide and also accelerates glucose disposal. It is suggested that furosemide acts via the release of endogenous PGEs, which are known to inhibit insulin responses in man.
Effects of Glucose on Insulin Release and on Intermediary Metabolism of Isolated Perifused Pancreatic Islets from Fed and Fasted Rats
Authors: Trus Michael , Warner Howard , Matschinsky Franz 
Published: September 2013

We examined the relationship between glucose-induced insulin release and the intermediary metabolism of islets from fed and fasted rats. Isolated islets were perifused and insulin release measured in the effluent. At various times after switching islets from 2.4 to 8.6 or 14.5 mM glucose or from 2.4 to 14.5 and back to 2.4 mM glucose, islets were quickly frozen, freeze dried, and subsequently analyzed for tissue content of glucose-6-P, fructose-1,6-P2 plus triose-P, P1, ATP, ADP, 5'-AMP, NADH, NADPH, total NAD, and total NADP using enzymatic fluorometric procedures. When islets from fed rats were exposed to high glucose, there were concomitant increases of insulin release and islet content of glucose-6-P, fructose-1,6-P2 plus triose-P, NADH, and NADPH. During stimulation P1 and 5'-AMP content fell markedly. The total adenine nucleotide content remained constant. Similar secretory and metabolic changes occurred when 1.5 mM P1 was added to the perifusion fluid. When glucose-stimulated islets were switched back to low glucose for 10 min, all substances but fructose-1,6-P2 plus triose-P, 5'-AMP, NADPH, and possibly ATP returned to the prestimulatory level. Starvation of rats for 3 days blocked the secretory response to 8.6 mM glucose. Fructose-1,6-P2 plus triose-P rose but it did not attain the level existing in islets from fed rats. The ratios (ATP)/(5'-AMP) and (ATP)/(P1,)(ADP) increased to the values observed in glucose-stimulated islets of fed rats.
The metabolic changes in islets from fed rats exposed to high glucose are consistent with an activation of glycolysis occurring concomitantly with stimulated rates of insulin release. This occurs despite the decrease of important activators of glycolysis—P1 and 5'-AMP. The enhanced glycolysis possibly results from P-fructokinase activation by increased fructose-6-P levels. Activation of glycolysis with 8.6 mM glucose was not as pronounced in islets from starved rats. Despite the different secretory response of islets from fed and fasted rats, the changes of phosphorylation state in the islets, in particular, P1, and 5'-AMP levels, were similar.
The Histocompatibility (HLA) Antigen Distribution in Diabetes in Southern African Blacks (Xhosa)
Authors: Briggs Brian R , Jackson W P U , DuToit Ernette D , Botha Martin C 
Published: September 2013

The frequency distributions of HLA antigens in 25 juvenile-onset diabetics (JOD) and 56 maturity-onset diabetics (MOD) belonging to a southern African black tribe (Xhosa) were compared with those of 153 non-diabetic Xhosa blacks. Unlike the findings in white JODs, there was no increase of B8 or B15 nor a reduced frequency of B7 but an apparently, significantly increased frequency of Bw35 and A2 in both Xhosa JODs and Xhosa MODs, respectively.
This is the first ethnic group in which an HLA antigen marker has been found for MOD. Furthermore, these findings suggest that diabetes, both JOD and MOD, in white people is a different genetic disease from the diabetes among the Xhosa tribe.
Alternatives in Pancreatic Islet Transplantation: Tissue Culture Studies
Authors: Reemtsma Keith , Weber Collin J , Pi-Sunyer F Xavier , Lerner Roger L , Hardy Mark A 
Published: September 2013

Culture Of Islets Isolated from the pancreas of neonatal rats successfully preserved function for 6 days, as indicated by release of insulin into the culture medium and reversal of experimental diabetes by cultured islet isografts. Release of insulin into the culture medium correlated with lowering of fasting blood glucose in the diabetic recipient. Intravenous glucose tolerance was normal in recipients of immediate and 24-h cultured islets but abnormal in recipients of 6-day cultured islets.
Culture of the islets isolated from human pancreases (cadaveric) resulted in islet purification but at the expense of loss of islets, with only 1–5% surviving 1 wk of culture. During 8–10 days in culture, insulin release declined, and histological examination revealed only a few viable islets. Islets isolated from surgical specimens survived the culture conditions as demonstrated by viable cell clumps and insulin secretion. After an 85% pancreatectomy in the patient with chronic pancreatitis, islets were isolated, cultured for 7 days, and then autografted into muscle pockets and the subcutaneous space of the forearm. There was no evidence of function.
Culture and Function in Vitro
Authors: Ågren A , Andersson A , Björkén C , Groth C G , Gunnarsson R , Hellerström C , Lindmark G , Lundqvist G , Petersson B , Swenne I 
Published: September 2013

Human fetal pancreas, obtained at prostaglandin-in-duced legal abortions, was maintained in organ culture for 6–14 days in medium TCM 199 (5.5 mM glucose) or RPMI 1640 (11.1 mM glucose) supplemented with 20% calf serum and antibiotics. Light microscopic examination indicated that the cultured explants were composed of fibrous tissue and well-preserved ducts and islets, whereas acinar cells had disappeared. The hormone content (insulin, C-peptide, glucagon, somatostatin) per milligram wet pancreatic weight increased 10–35 times during the culture period.
In static incubations of cultured explants there was a poor insulin response to glucose (16.7 mM). By contrast, insulin release was markedly stimulated in the presence of both glucose (16.7 mM) and theophylline (10 mM). The maximal rate of insulin release in response to glucose plus theophylline was observed after 11 days of culture. When pancreatic explants were incubated in a perifusion system after 7 days in culture, 25% of the fetuses showed a low and monophasic insulin response to glucose alone (15 mM), whereas the remaining ones failed to respond. When perifusions were performed with glucose (15 mM) plus theophylline (5 mM), the insulin response was high in about 25% of the fetuses, intermediate in 40%, and low in 35%. Neither in the static incubations nor in the perifusions was there any clear correlation between the rates of insulin release and the tissue culture medium used.
It is concluded that human fetal B cells may retain viability in organ culture for more than a week. The fetal pancreatic material prepared and stored by this means may be used in attempts to cure human diabetes by transplantation.
Transplantation of Human Fetal Pancreas: Experience in Thymusaplastic Mice and Rats and in a Diabetic Patient
Authors: Usadel K H , Schwedes U , Bastert G , Steinau U , Klempa I , Fassbinder W , Schöffling K 
Published: September 2013

The aim of the present study was to investigate if thymusaplastic nude mice and rats are favorable as recipients for transplantation of human fetal pancreas. Twenty human fetal pancreases were transplanted subcutaneously to 20 nude mice, and six human fetal pancreases were transplanted to six rats. The xenografts showed histotypical development of islets of Langerhans. Insulin, glucagon, somatostatin, and pancreatic polypeptide immunoreactivities were also seen in very early stages of the transplant development within the monolayered ducts.
With the described “epigastric pouch technique” in rats, we could demonstrate a new in vivo method for selective stimulations and simultaneous blood sampling from tissue-isolated xenografts.
Transplantation of human fetal pancreas to the brachioradial muscle of an insulin-dependent patient in combination with a kidney transplant revealed that rejection crises of the kidney led to necrosis of the pancreas transplant, whereas rejection of the kidney was overcome by steroid pulse therapy.