Insulin secretion and intestinal peptides during lactation in sheep

1999 ◽  
Vol 66 (1) ◽  
pp. 45-52 ◽  
Author(s):  
ANNE FAULKNER ◽  
PAMELA A. MARTIN
Keyword(s):  
Insulin Secretion ◽  
Plasma Glucose ◽  
Serum Insulin ◽  
Inhibitory Effects ◽  
Significant Difference ◽  
Intestinal Peptides ◽  
Increased Sensitivity ◽  
Glucagon Like Peptide 1 ◽  
The Difference ◽  
Glucose Stimulated Insulin Secretion

Intravenous infusions of glucose and/or glucagon-like peptide-1(7–36)-amide (GLP) or somatostatin-28 (S28) were administered to dry and lactating sheep and changes in plasma glucose and serum insulin were followed before, during and after infusion. Basal serum insulin concentrations were significantly lower in lactating sheep but there was no significant difference in plasma glucose concentrations. During glucose infusion, changes in serum insulin concentrations were diminished by comparison with those in dry animals. GLP stimulated insulin secretion during hyperglycaemia in both dry and lactating sheep but, proportionately, the response was significantly greater in the lactating animals. S28 inhibited glucose-stimulated insulin secretion in both dry and lactating sheep and there was no significant difference in the extent of the inhibition between the two physiological states. S28 infusion also inhibited the secretion of GLP from the intestinal tract and this effect was significantly greater in the lactating animals. The results demonstrate a difference in response in the lactating animal to GLP compared with S28. A possible explanation of the difference is a decreased sensitivity (i.e. increased Km) of the pancreas to the insulinotropic effects of GLP but an increased sensitivity to the inhibitory effects of S28 at tissues other than the pancreas in lactation.

scholarly journals Subthreshold α2-Adrenergic Activation Counteracts Glucagon-Like Peptide-1 Potentiation of Glucose-Stimulated Insulin Secretion

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Minglin Pan ◽  
Guang Yang ◽  
Xiuli Cui ◽  
Shao-Nian Yang
Keyword(s):  
Insulin Secretion ◽  
Insulin Release ◽  
Adrenergic Agonist ◽  
Signaling Systems ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Glucose Stimulated Insulin Secretion ◽  
Insulin Secretory Response ◽  
Adrenergic Activation ◽  
Gi Proteins

The pancreatic β cell harbors α2-adrenergic and glucagon-like peptide-1 (GLP-1) receptors on its plasma membrane to sense the corresponding ligands adrenaline/noradrenaline and GLP-1 to govern glucose-stimulated insulin secretion. However, it is not known whether these two signaling systems interact to gain the adequate and timely control of insulin release in response to glucose. The present work shows that the α2-adrenergic agonist clonidine concentration-dependently depresses glucose-stimulated insulin secretion from INS-1 cells. On the contrary, GLP-1 concentration-dependently potentiates insulin secretory response to glucose. Importantly, the present work reveals that subthreshold α2-adrenergic activation with clonidine counteracts GLP-1 potentiation of glucose-induced insulin secretion. This counteractory process relies on pertussis toxin- (PTX-) sensitive Gi proteins since it no longer occurs following PTX-mediated inactivation of Gi proteins. The counteraction of GLP-1 potentiation of glucose-stimulated insulin secretion by subthreshold α2-adrenergic activation is likely to serve as a molecular mechanism for the delicate regulation of insulin release.

scholarly journals Transgenic Expression of Glucagon-Like Peptide-1 (GLP-1) and Activated Muscarinic Receptor (M3R) Significantly Improves Pig Islet Secretory Function

2017 ◽  
Vol 26 (5) ◽  
pp. 901-911 ◽  
Author(s):  
Nizar I. Mourad ◽  
Andrea Perota ◽  
Daela Xhema ◽  
Cesare Galli ◽  
Pierre Gianello
Keyword(s):  
Insulin Secretion ◽  
Muscarinic Receptor ◽  
Expression Vectors ◽  
Specific Expression ◽  
Transgenic Expression ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Glucose Stimulated Insulin Secretion ◽  
Type 3

Porcine islets show notoriously low insulin secretion levels in response to glucose stimulation. While this is somehow expected in the case of immature islets isolated from fetal and neonatal pigs, disappointingly low secretory responses are frequently reported in studies using in vitro-maturated fetal and neonatal islets and even fully differentiated adult islets. Herein we show that β-cell-specific expression of a modified glucagon-like peptide-1 (GLP-1) and of a constitutively activated type 3 muscarinic receptor (M3R) efficiently amplifies glucose-stimulated insulin secretion (GSIS). Both adult and neonatal isolated pig islets were treated with adenoviral expression vectors carrying sequences encoding for GLP-1 and/or M3R. GSIS from transduced and control islets was evaluated during static incubation and dynamic perifusion assays. While expression of GLP-1 did not affect basal or stimulated insulin secretion, activated M3R produced a twofold increase in both first and second phases of GSIS. Coexpression of GLP-1 and M3R caused an even greater increase in the secretory response, which was amplified fourfold compared to controls. In conclusion, our work highlights pig islet insulin secretion deficiencies and proposes concomitant activation of cAMP-dependent and cholinergic pathways as a solution to ameliorate GSIS from pig islets used for transplantation.

scholarly journals Investigation of Fasting Plasma Glucose in Masters Athletes

2020 ◽  
Vol 4 (2) ◽  
pp. 65-68
Author(s):  
Joe Walsh ◽  
◽  
Ian Timothy Heazlewood ◽  
Mark DeBeliso ◽  
Mike Climstein ◽  
...  
Keyword(s):  
Plasma Glucose ◽  
Fasting Plasma Glucose ◽  
Sport Participation ◽  
Past Research ◽  
Fasting Plasma ◽  
Age Related ◽  
Significant Difference ◽  
Masters Athletes ◽  
The Mean ◽  
The Difference

Prior research documented differences in fasting plasma glucose (FPG) between older and younger masters athletes at the Golden Oldies Rugby Festival (GORF). It was the purpose of our study to further investigate FPG on a larger sample. FPG data was collected on 486 participants at the Sydney World Masters Games. Of the males, 241 reported optimal FPG and 36 reported sub-optimal FPG. For females 183 reported optimal FPG and 26 reported sub-optimal FPG. Analysis was conducted utilising the age ranges implemented in past research on the GORF. The mean FPG for masters athletes below 50 years old was 5.10±1.52 mmol/L, whilst for those 50 years and above it was 5.01±1.02. The difference between the groups was not significant (t = 0.722, p = 0.471). This aligned with the finding of the GORF study that there was no significant difference in FPG between the different age ranges analysed. The sample size obtained for this investigation of FPG in masters athletes was more than double the number of participants used in previous research on the GORF. Many participants had FPG above optimal levels. Therefore, an age-related decline in pancreatic function may outweigh protective exercise benefits attained from masters sport participation.

scholarly journals Emerging role of testosterone in pancreatic β cell function and insulin secretion

2019 ◽  
Vol 240 (3) ◽  
pp. R97-R105 ◽  
Author(s):  
Weiwei Xu ◽  
Jamie Morford ◽  
Franck Mauvais-Jarvis
Keyword(s):  
Insulin Secretion ◽  
Metabolic Regulation ◽  
Cell Function ◽  
Visceral Obesity ◽  
Β Cells ◽  
Β Cell ◽  
Β Cell Function ◽  
Glucagon Like Peptide 1 ◽  
Glucose Stimulated Insulin Secretion

One of the most sexually dimorphic aspects of metabolic regulation is the bidirectional modulation of glucose homeostasis by testosterone in male and females. Severe testosterone deficiency predisposes men to type 2 diabetes (T2D), while in contrast, androgen excess predisposes women to hyperglycemia. The role of androgen deficiency and excess in promoting visceral obesity and insulin resistance in men and women respectively is well established. However, although it is established that hyperglycemia requires β cell dysfunction to develop, the role of testosterone in β cell function is less understood. This review discusses recent evidence that the androgen receptor (AR) is present in male and female β cells. In males, testosterone action on AR in β cells enhances glucose-stimulated insulin secretion by potentiating the insulinotropic action of glucagon-like peptide-1. In females, excess testosterone action via AR in β cells promotes insulin hypersecretion leading to oxidative injury, which in turn predisposes to T2D.

Beta-cell sensitivity to insulinotropic gut hormones is reduced after gastric bypass surgery

Gut ◽  
2019 ◽  
Vol 68 (10) ◽  
pp. 1838-1845 ◽  
Author(s):  
Marzieh Salehi ◽  
Amalia Gastaldelli ◽  
David A D’Alessio
Keyword(s):  
Gastric Bypass ◽  
Insulin Secretion ◽  
Gastric Bypass Surgery ◽  
Gut Hormones ◽  
Normal Glucose Tolerance ◽  
Cell Sensitivity ◽  
Glucose Levels ◽  
Normal Glucose ◽  
Glucagon Like Peptide 1 ◽  
Glucose Stimulated Insulin Secretion

ObjectivePostprandial hyperinsulinaemia after Roux-en Y gastric bypass (GB) has been attributed to rapid nutrient flux from the gut, and an enhanced incretin effect. However, it is unclear whether surgery changes islet cell responsiveness to regulatory factors. This study tested the hypothesis that β-cell sensitivity to glucagon like-peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) is attenuated after GB.DesignTen non-diabetic subjects with GB, and 9 body mass index (BMI)-matched and age-matched non-surgical controls (CN) with normal glucose tolerance had blood glucose clamped at ~7.8 mM on three separate days. Stepwise incremental infusions of GLP-1 (15, 30, 60, 120 and 300 ng/LBkg/h), GIP (75, 150, 300, 600 and 1200 ng/LBkg/h) or saline were administered from 90 to 240 min and insulin secretion measured.ResultsGB subjects had similar fasting glucose levels but lower fasting insulin compared with CN, likely due to increased insulin clearance. The average insulin secretion rates (ISRs) to 7.8 mM glucose were ~30% lower in GB relative to CN subjects. However, incretin-stimulated ISRs, adjusted for insulin sensitivity and glucose-stimulated insulin secretion, were even more attenuated in the GB subjects, by threefold to fourfold (AUCISR(90−240 min) during GLP-1 and GIP: 47±8 and 44±12 nmol in GB and 116±16 and 161±44 in CN; p<0.01).ConclusionAfter GB, the sensitivity of insulin secretion to both glucose and incretins is diminished.

Peptide YY does not inhibit glucose-stimulated insulin secretion in humans

1996 ◽  
Vol 134 (3) ◽  
pp. 362-365 ◽  
Author(s):  
Bo Ahrén ◽  
Hillevi Larsson
Keyword(s):  
Insulin Secretion ◽  
Peptide Yy ◽  
Serum Insulin ◽  
Elimination Rate ◽  
Insulin Response ◽  
University Hospital ◽  
High Rate ◽  
Laboratory Animals ◽  
Gut Hormone ◽  
Glucose Stimulated Insulin Secretion

Ahrén B, Larsson H. Peptide YY does not inhibit glucose-stimulated insulin secretion in humans. Eur J Endocrinol 1996;134:362–5. ISSN 0804–4643 Peptide YY (PYY) is localized to gut and pancreatic endocrine cells. It may therefore be involved in the regulation of insulin secretion as a gut hormone as well as an islet local regulator. In laboratory animals, the peptide inhibits stimulated insulin secretion, but its effects in humans are not known. We therefore infused PYY intravenously at a low (1 pmol·kg−1 · min−1; N = 4) or a high rate (5 pmol · kg−1 · min−1; N= 5) for 120 min in healthy women aged 52 years. After 30 min of infusion, glucose (0.5 g/kg) was injected rapidly. In separate control experiments, saline was infused instead of PYY. We found that PYY did not inhibit the acute insulin response to glucose or affect the glucose elimination rate, and PYY was also without influence on the basal plasma glucose and serum insulin levels during the 30-min infusion before the challenge with glucose. We therefore conclude that intravenous infusion of PYY does not affect glucose-stimulated insulin secretion in man. Bo Ahrén, Department of Medicine, Malmö University Hospital, S-205 02 Malmö, Sweden

scholarly journals GIP and GLP-1 Potentiate Sulfonylurea-Induced Insulin Secretion in Hepatocyte Nuclear Factor 1-Alpha Mutation Carriers

2020 ◽  
Author(s):  
Ada Admin ◽  
Alexander S. Christensen ◽  
Sofie Hædersdal ◽  
Heidi Storgaard ◽  
Kathrine Rose ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucagon Secretion ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Mutation Carriers ◽  
Glucagon Like Peptide 1 ◽  
Glucose Stimulated Insulin Secretion ◽  
Nuclear Factor 1 ◽  
Double Blinded ◽  
Insulinotropic Peptide

Sulfonylureas (SUs) provide an efficacious first-line treatment in patients with hepatocyte nuclear factor 1-alpha (HNF1A)-diabetes, but SUs have limitations due to risk of hypoglycemia. Treatment based on the incretin hormones, glucose-dependent insulinotropic peptide (GIP) and glucagon-like-peptide 1 (GLP-1), are characterized by their glucose-dependent insulinotropic actions without risk of hypoglycemia. The effect of SUs together with GIP or GLP-1, respectively, on insulin and glucagon secretion in patients with HNF1A-diabetes is currently unknown. To investigate this, ten <i>HNF1A </i>mutation carriers and ten non-diabetic controls were recruited for a double-blinded, placebo-controlled, crossover study including six experimental days in a randomized order involving 2h euglycemic-hyperglycemic clamps with co-administration of 1) SU (glimepiride 1 mg) or placebo, combined with 2) infusions of either GIP (1.5 pmol/kg/min), GLP-1 (0.5 pmol/kg/min) or saline (NaCl). In <i>HNF1A </i>mutation carriers we observed: 1) hypoinsulinemia, 2) insulinotropic effects of both GIP and GLP-1, 3) <a>additive to supra-additive effects on insulin secretion when combining SU+GIP and SU+GLP1, respectively, </a>and 4) increased fasting and arginine-induced glucagon levels compared to non-diabetic controls. Our study suggests that a combination of SU and incretin-based treatment may be efficacious in patients with HNF1A-diabetes via potentiation of glucose-stimulated insulin secretion.

Sign in / Sign up

Export Citation Format

Share Document