α- and β-Cell Function in Obese Zucker (fa/fa) Rats: A Study with the Isolated Perfused Pancreas

1994 ◽  
Vol 86 (3) ◽  
pp. 311-316 ◽  
Author(s):  
Dr Hiroshi Hirose ◽  
Hiroshi Maruyama ◽  
Koichi Kido ◽  
Katsuhiko Ito ◽  
Kazunori Koyama ◽  
...  
Keyword(s):  
Glucose Concentration ◽  
Cell Function ◽  
Glucagon Secretion ◽  
Zucker Rats ◽  
Perfused Pancreas ◽  
Isolated Perfused Pancreas ◽  
Insulin And Glucagon Secretion ◽  
Β Cell Function ◽  
Insulin Secretion Rate ◽  
Insulin Secretory Response

1. The effects of various stimuli, including changes in glucose concentration, arginine, tyramine and noradrenaline, on insulin and glucagon secretion were investigated using isolated perfused pancreata of obese and lean male Zucker rats at 12 months of age. 2. In Zucker fatty rats, the insulin secretion rate was significantly (P < 0.01) higher than that of lean rats at all glucose concentrations tested (8.3, 16.7 and 1.4 mmol/l). However, the integrated insulin secretory response to raising the glucose concentration from 8.3 to 16.7 mmol/l was almost absent in these rats. The glucagon secretion rates were significantly lower at 8.3 and 1.4 mmol/l glucose (P < 0.001 for both), and in responses to 10 μg/ml tyramine and 0.1 μmol/l noradrenaline (P < 0.05 for both), in Zucker fatty rats. Integrated insulin and glucagon responses to 10 mmol/l arginine were identical in the two groups. 3. Histopathological and immunochemical studies revealed hyperplasia of β-cells and scattered α-cells in the enlarged islets of Zucker fatty rats. 4. These results suggest that, in Zucker fatty rats, the decreased glucagon secretion in the isolated perfused pancreas is attributable to changes in the environment of α-cells and/or the inhibitory effects of hypersecreted insulin.

Impact of lack of suppression of glucagon on glucose tolerance in humans

1999 ◽  
Vol 277 (2) ◽  
pp. E283-E290 ◽  
Author(s):  
Pankaj Shah ◽  
Ananda Basu ◽  
Rita Basu ◽  
Robert Rizza
Keyword(s):  
Insulin Secretion ◽  
Glucose Concentration ◽  
Cell Function ◽  
Hormone Secretion ◽  
Glucose Production ◽  
Glucagon Secretion ◽  
Β Cell ◽  
Β Cell Function ◽  
Glucagon Suppression

People with type 2 diabetes have defects in both α- and β-cell function. To determine whether lack of suppression of glucagon causes hyperglycemia when insulin secretion is impaired but not when insulin secretion is intact, twenty nondiabetic subjects were studied on two occasions. On both occasions, a “prandial” glucose infusion was given over 5 h while endogenous hormone secretion was inhibited. Insulin was infused so as to mimic either a nondiabetic ( n = 10) or diabetic ( n = 10) postprandial profile. Glucagon was infused at a rate of 1.25 ng ⋅ kg−1 ⋅ min−1, beginning either at time zero to prevent a fall in glucagon (nonsuppressed study day) or at 2 h to create a transient fall in glucagon (suppressed study day). During the “diabetic” insulin profile, lack of glucagon suppression resulted in a marked increase ( P < 0.002) in both the peak glucose concentration (11.9 ± 0.4 vs. 8.9 ± 0.4 mmol/l) and the area above basal of glucose (927 ± 77 vs. 546 ± 112 mmol ⋅ l−1 ⋅ 6 h) because of impaired ( P < 0.001) suppression of glucose production. In contrast, during the “nondiabetic” insulin profile, lack of suppression of glucagon resulted in only a slight increase ( P< 0.02) in the peak glucose concentration (9.1 ± 0.4 vs. 8.4 ± 0.3 mmol/l) and the area above basal of glucose (654 ± 146 vs. 488 ± 118 mmol ⋅ l−1 ⋅ 6 h). Of interest, when glucagon was suppressed, glucose concentrations differed only minimally during the nondiabetic and diabetic insulin profiles. These data indicate that lack of suppression of glucagon can cause substantial hyperglycemia when insulin availability is limited, therefore implying that inhibitors of glucagon secretion and/or glucagon action are likely to be useful therapeutic agents in such individuals.

Somatostatin, insulin, and glucagon secretion from isolated perfused pancreas of obese rats

1981 ◽  
Vol 241 (2) ◽  
pp. E146-E150
Author(s):  
S. Seino ◽  
Y. Seino ◽  
J. Takemura ◽  
K. Tsuda ◽  
H. Kuzuya ◽  
...  
Keyword(s):  
Hormone Secretion ◽  
Glucagon Secretion ◽  
Ventromedial Hypothalamus ◽  
Perfused Pancreas ◽  
Isolated Perfused Pancreas ◽  
Insulin And Glucagon Secretion ◽  
Perfusion Experiment ◽  
Pancreatic Hormone ◽  
And Control

A comparison of the somatostatin with the insulin and glucagon secretions in hypothalamic obesity and genetic obesity was made using the isolated perfused pancreas of rats. In our perfusion experiment, the somatostatin response to 19 mM arginine in the presence of 4.4 mM glucose was significantly greater in both ventromedial hypothalamus (VMH)-lesioned and Zucker fa/fa rats than in their controls, as was the perfusate insulin. The perfusate arginine-stimulated glucagon secretion appeared no different in obese and control rats. Because hyperinsulinemia in vivo and hyperresponses to arginine of perfusate insulin and somatostatin were observed in both VMH-lesioned and Zucker fa/fa rats, whereas the perfusate glucagon secretion in the presence of 4.4 mM glucose was unchanged by obesity, the secretory behavior of some pancreatic hormones seems similar in VMH-lesioned and Zucker fa/fa rats in certain conditions. These results suggest that some abnormalities of pancreatic hormone secretion may be caused by a mechanism common to obesity, whether caused experimentally or genetically.

Somatostatin, insulin and glucagon secretion by the perfused pancreas from the cysteamine-treated rat

1986 ◽  
Vol 134 (3) ◽  
pp. 1291-1297 ◽  
Author(s):  
R.A. Silvestre ◽  
P. Miralles ◽  
P. Moreno ◽  
M.L. Villanueva ◽  
J. Marco
Keyword(s):  
Glucagon Secretion ◽  
Perfused Pancreas ◽  
Insulin And Glucagon Secretion

Improved β-cell function after standardized weight reduction in severely obese subjects

2003 ◽  
Vol 284 (3) ◽  
pp. E557-E565 ◽  
Author(s):  
Marie Guldstrand ◽  
Bo Ahrén ◽  
Ulf Adamson
Keyword(s):  
Insulin Sensitivity ◽  
Weight Reduction ◽  
Cell Function ◽  
Insulin Response ◽  
Insulin Level ◽  
Glucagon Secretion ◽  
Obese Women ◽  
Β Cell ◽  
Β Cell Function ◽  
Severely Obese

Islet function was examined in 13 severely obese women [body mass index 46.4 ± 5.5 (SD) kg/m2] before and after standardized 15 and 25% weight reduction (WR) instituted by bariatric surgery. The insulin response to arginine at fasting (AIR1), at 14 mmol/l, and at >25 mmol/l glucose was reduced by 37–50% after 15 and 25% WR ( P ≤ 0.05). Insulin sensitivity was determined as the amount of glucose infused to reach 14 mmol/l divided by the insulin level (M/I), a measure showing a linear correlation with insulin sensitivity during euglycemic hyperinsulinemic clamps ( r = 0.74, P < 0.001) and a hyperbolic relation to AIR1 ( r = −0.63, P < 0.001) in 169 healthy subjects. M/I was increased by 318 ± 182% after 15% ( P = 0.004) and by 489 ± 276% after 25% WR ( P = 0.007). The reduction in insulin secretion was not as large as anticipated from the increased insulin sensitivity, which resulted in an increased disposition index (DI; AIR1 × M/I). Thus DI increased by 95 ± 24% after 15% ( P = 0.018) and by 176 ± 35% after 25% WR ( P = 0.011). This improved β-cell function correlated independently with reduced glucose, triglycerides, and leptin and increased adiponectin levels and was associated with a reduced proinsulin-to-insulin ratio. In contrast, glucagon secretion was not significantly affected by WR. We conclude that WR results in improved β-cell function when related to insulin sensitivity.

scholarly journals Mechanisms of action of a carbohydrate-reduced, high-protein diet in reducing the risk of postprandial hypoglycemia after Roux-en-Y gastric bypass surgery

2019 ◽  
Vol 110 (2) ◽  
pp. 296-304 ◽  
Author(s):  
Daniel Kandel ◽  
Kirstine Nyvold Bojsen-Møller ◽  
Maria Saur Svane ◽  
Amirsalar Samkani ◽  
Arne Astrup ◽  
...  
Keyword(s):  
Gastric Bypass ◽  
Insulin Secretion ◽  
Cell Function ◽  
Gastric Bypass Surgery ◽  
High Protein Diet ◽  
Glucagon Secretion ◽  
Glucose Variability ◽  
High Protein ◽  
Β Cell Function ◽  
Glucagon Like Peptide 1

ABSTRACT Background Postprandial hypoglycemia is a risk after Roux-en-Y gastric bypass (RYGB). Objectives We speculated that a carbohydrate-reduced, high-protein (CRHP) diet might reduce the risk of hypoglycemia and therefore compared the acute effects of a conventionally recommended (CR) diet and CRHP diet [55/30 energy percent (E%) carbohydrate and 15/30 E% protein, respectively] in RYGB patients. Methods Ten individuals (2 males, 8 females, mean ± SD age 47 ± 7 y; stable body mass index 31 ± 6 kg/m2; 6 ± 3 y post-RYGB) with recurrent postprandial hypoglycemia documented by plasma glucose (PG) ≤3.4 mmol/L were examined on 2 d with isoenergetic CRHP or CR diets comprising a breakfast and subsequent lunch meal. Results Peak PG was significantly reduced on the CRHP diet after breakfast and lunch by 11% and 31% compared with the CR diet. Nadir PG increased significantly on CRHP (by 13% and 9%). Insulin secretion was reduced, and glucagon secretion increased on the CRHP diet after both meals. Glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide secretion were lower after lunch but unaltered after breakfast on CRHP; β-cell function and insulin clearance were unchanged. Conclusions The CRHP diet lowered glucose excursions and reduced insulin secretion and incretin hormone responses, but enhanced glucagon responses compared with the CR diet. Taken together, the results may explain the decreased glucose variability and lower risk of postprandial hypoglycemia. This study was registered at clinicaltrials.gov as NCT02665715.

Vildagliptin An Oral Dipeptidyl Peptidase-4 Inhibitor for Type 2 Diabetes

2006 ◽  
Vol 00 (02) ◽  
Author(s):  
Eberhard Standl ◽  
Martin Fuchtenbusch ◽  
Michael Hummel
Keyword(s):  
Type 2 Diabetes ◽  
Large Scale ◽  
Cell Function ◽  
Glucagon Secretion ◽  
Postprandial Glucose ◽  
Dipeptidyl Peptidase ◽  
Β Cell ◽  
Dipeptidyl Peptidase 4 ◽  
Β Cell Function

Vildagliptin is a member of a new class of oral antidiabetogenic agents known as dipeptidyl peptidase-4 (DDP-4) inhibitors.These drugs enhance islet function by improving α- and β-cell responsiveness to glucose. Mechanism of action studies in patients with type 2 diabetes show that vildagliptin increases plasma levels of active glucagon-like peptide-1, improves glucosedependent insulin secretion and β-cell function, improves insulin sensitivity, reduces inappropriate glucagon secretion, reduces fasting and postprandial glucose, and decreases HbA1c. Large-scale treatment trials with vildagliptin 50mg or 100mg per day as monotherapy or in combination in drug-naïve patients or as add-on therapy to on-going anti-diabetic treatment show that it is effective in reducing HbA1c (with greater decreases occurring in patients with higher initial HbA1c levels), maintains efficacy in glycemic control as monotherapy for at least 1 year, is associated with infrequent hypoglycemia, and does not cause weight gain.

Interleukin-1 potentiates glucose stimulated insulin release in the isolated perfused pancreas

1988 ◽  
Vol 117 (3) ◽  
pp. 302-306 ◽  
Author(s):  
Lise D. Wogensen ◽  
Thomas Mandrup-Poulsen ◽  
Helle Markholst ◽  
Jens Mølvig ◽  
Åke Lernmark ◽  
...  
Keyword(s):  
Insulin Release ◽  
Cell Function ◽  
Interleukin 1 ◽  
Systemic Circulation ◽  
Second Phase ◽  
Interleukin 1 Beta ◽  
Perfused Pancreas ◽  
Porcine Pancreas ◽  
Isolated Perfused Pancreas

Abstract. The acute effects of recombinant human interleukin-1 beta (rIL-1) on basal and glucose-stimulated insulin release were investigated in the isolated perfused pancreas. At a concentration of 20 μg/l rIL-1 had no effect on basal insulin release, but increased the total amount of insulin released during first and second phase insulin release in response to 20 mmol/l D-glucose in the rat pancreas (P < 0.05). In addition, 26 μg/l of rIL-1 potentiated insulin release in response to square wave infusions of stimulatory concentrations of glucose (11 mmol/l) in the porcine pancreas. We hypothesize that IL-1 in the systemic circulation may affect B cell function in vivo.

PANCREATIC β-CELL FUNCTION IN THE FETAL FOAL AND MARE

1980 ◽  
Vol 87 (2) ◽  
pp. 293-301 ◽  
Author(s):  
ABIGAIL L. FOWDEN ◽  
R. J. BARNES ◽  
R. S. COMLINE ◽  
MARIAN SILVER
Keyword(s):  
Gestational Age ◽  
Glucose Concentration ◽  
Cell Function ◽  
Insulin Concentration ◽  
Β Cell ◽  
Exogenous Glucose ◽  
Β Cell Function ◽  
The Mean ◽  
Mean Glucose ◽  
Mean Concentration

Insulin secretion and the factors influencing β-cell function were investigated in the chronically catheterized fetal foal and mare during the second half of gestation. The response of the fetal β cells to exogenous glucose was also examined. The mean concentration of insulin in the fetal foal was 7·5 ± 0·5 (s.e.m.) μu./ml (n = 20) which was significantly less than the corresponding maternal value of 49·0 ± 5·0μu./ml (n = 20, P<0·01). The insulin concentration in non-pregnant horses was 24·5 ± 1·5 μu./ml (n = 5) which was significantly less than the value in the pregnant animals (P<0·01). However, there was no significant difference in the mean glucose concentration between the groups of adult animals. The insulin concentration was related to the endogenous glucose level in both adult and fetal horses. Wide variation in the maternal insulin concentration was observed above a glucose concentration of about 5·0 mmol/l. The mean concentration of insulin in pregnant mares decreased with increasing gestational age while the mean glucose concentration remained unaltered throughout the second half of gestation. There was no change in the basal concentrations of insulin or glucose in the fetus with gestational age although the fetal β-cell response to exogenous glucose appeared to increase with increasing fetal age after 270 days of gestation (term 330 days). There was a significant arterio-venous difference in the concentration of insulin across the gravid uterus in the mare when the arterial insulin level was greater than 30 μu./ml. Below this value, there was no consistent uptake of insulin by the uterus. The observations are discussed in relation to the regulation of insulin release in utero and the effects of pregnancy on maternal β-cell function.

scholarly journals Upregulated insulin secretion in insulin-resistant mice: evidence of increased islet GLP1 receptor levels and GPR119-activated GLP1 secretion

2013 ◽  
Vol 2 (2) ◽  
pp. 69-78 ◽  
Author(s):  
L Ahlkvist ◽  
K Brown ◽  
B Ahrén
Keyword(s):  
Cell Function ◽  
Hormone Secretion ◽  
Glucagon Secretion ◽  
Β Cell ◽  
Insulin Resistant ◽  
Protein Levels ◽  
Islet Hormone ◽  
Β Cell Function ◽  
Glucagon Like Peptide 1 ◽  
Insulin Responses

We previously demonstrated that the overall incretin effect and the β-cell responsiveness to glucagon-like peptide-1 (GLP1) are increased in insulin-resistant mice and may contribute to the upregulated β-cell function. Now we examined whether this could, first, be explained by increased islet GLP1 receptor (GLP1R) protein levels and, secondly, be leveraged by G-protein-coupled receptor 119 (GPR119) activation, which stimulates GLP1 secretion. Female C57BL/6J mice, fed a control (CD, 10% fat) or high-fat (HFD, 60% fat) diet for 8 weeks, were anesthetized and orally given a GPR119 receptor agonist (GSK706A; 10 mg/kg) or vehicle, followed after 10 min with gavage with a liquid mixed meal (0.285 kcal). Blood was sampled for determination of glucose, insulin, intact GLP1, and glucagon, and islets were isolated for studies on insulin and glucagon secretion and GLP1R protein levels. In HFD vs CD mice, GPR119 activation augmented the meal-induced increase in the release of both GLP1 (AUCGLP1 81±9.6 vs 37±6.9 pM×min, P=0.002) and insulin (AUCINS 253±29 vs 112±19 nM×min, P<0.001). GPR119 activation also significantly increased glucagon levels in both groups (P<0.01) with, however, no difference between the groups. By contrast, GPR119 activation did not affect islet hormone secretion from isolated islets. Glucose elimination after meal ingestion was significantly increased by GPR119 activation in HFD mice (0.57±0.04 vs 0.43±0.03% per min, P=0.014) but not in control mice. Islet GLP1R protein levels was higher in HFD vs CD mice (0.8±0.1 vs 0.5±0.1, P=0.035). In conclusion, insulin-resistant mice display increased islet GLP1R protein levels and augmented meal-induced GLP1 and insulin responses to GPR119 activation, which results in increased glucose elimination. We suggest that the increased islet GLP1R protein levels together with the increased GLP1 release may contribute to the upregulated β-cell function in insulin resistance.

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