Secretion of the Incretin Hormones Glucagon-Like Peptide-1 and Gastric Inhibitory Polypeptide Correlates with Insulin Secretion in Normal Man Throughout the Day

1996 ◽  
Vol 31 (7) ◽  
pp. 665-670 ◽  
Author(s):  
C. Ørskov ◽  
A. Wettergren ◽  
J. J. Holst
Keyword(s):  
Insulin Secretion ◽  
Gastric Inhibitory Polypeptide ◽  
Incretin Hormones ◽  
Normal Man ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals Increased insulin clearance in mice with double deletion of glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptors

2018 ◽  
Vol 314 (5) ◽  
pp. R639-R646 ◽  
Author(s):  
Andrea Tura ◽  
Roberto Bizzotto ◽  
Yuchiro Yamada ◽  
Yutaka Seino ◽  
Giovanni Pacini ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Clearance ◽  
Second Phase ◽  
Incretin Hormones ◽  
Intravenous Glucose ◽  
C Peptide ◽  
Double Deletion ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
First Phase Insulin Secretion

To establish whether incretin hormones affect insulin clearance, the aim of this study was to assess insulin clearance in mice with genetic deletion of receptors for both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), so called double incretin receptor knockout mice (DIRKO). DIRKO ( n = 31) and wild-type (WT) C57BL6J mice ( n = 45) were intravenously injected with d-glucose (0.35 g/kg). Blood was sampled for 50 min and assayed for glucose, insulin, and C-peptide. Data were modeled to calculate insulin clearance; C-peptide kinetics was established after human C-peptide injection. Assessment of C-peptide kinetics revealed that C-peptide clearance was 1.66 ± 0.10 10−3 1/min. After intravenous glucose administration, insulin clearance during first phase insulin secretion was markedly higher in DIRKO than in WT mice (0.68 ± 0.06 10−3 l/min in DIRKO mice vs. 0.54 ± 0.03 10−3 1/min in WT mice, P = 0.02). In contrast, there was no difference between the two groups in insulin clearance during second phase insulin secretion ( P = 0.18). In conclusion, this study evaluated C-peptide kinetics in the mouse and exploited a mathematical model to estimate insulin clearance. Results showed that DIRKO mice have higher insulin clearance than WT mice, following intravenous injection of glucose. This suggests that incretin hormones reduce insulin clearance at physiological, nonstimulated levels.

DPP-4 Inhibition as a Newly Emerging Therapy for Type 2 Diabetes

2006 ◽  
Vol 00 (02) ◽  
Author(s):  
Carolyn F Deacon ◽  
Jens Juul Holst
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Progressive Disease ◽  
Incretin Hormones ◽  
New Approach ◽  
Current Therapies ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Emerging Therapy

Type 2 diabetes mellitus (T2DM) is a progressive disease, characterized by insulin resistance, impaired glucose-induced insulin secretion, inappropriately elevated glucagon concentrations, and hyperglycemia. Many patients cannot obtain satisfactory glycemic control with current therapies, and eventually develop microvascular and macrovascular diabetic complications. New and more effective agents, targeted not only at treatment, but also at prevention of the disease, its progression, and its associated complications, are, therefore, required. One new approach focuses on the effects of the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which enhance mealinduced insulin secretion.1

PACAP contributes to insulin secretion after gastric glucose gavage in mice

2000 ◽  
Vol 279 (2) ◽  
pp. R424-R432 ◽  
Author(s):  
Karin Filipsson ◽  
Jens Juul Holst ◽  
Bo Ahrén
Keyword(s):  
Insulin Secretion ◽  
Insulin Response ◽  
Gastric Inhibitory Polypeptide ◽  
Inhibitory Effect ◽  
Intravenous Glucose ◽  
Parasympathetic Nerves ◽  
Prandial Insulin ◽  
Pituitary Adenylate Cyclase ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Pituitary adenylate cyclase-activating polypeptide (PACAP) is localized to pancreatic ganglia governing the parasympathetic nerves, which contribute to prandial insulin secretion. We hypothesized that this contribution involves PACAP and show here that the PACAP receptor antagonist PACAP-(6—27) (1.5 nmol/kg iv) reduces the 15-min insulin response to gastric glucose (150 mg/mouse) by 18% in anesthetized mice ( P = 0.041). The reduced insulinemia was not due to inhibited release of the incretin factor glucagon-like peptide 1 (GLP-1) because PACAP-(6—27) enhanced the GLP-1 response to gastric glucose. Furthermore, the GLP-1 antagonist exendin-3-(9—39) (30 nmol/kg) exerted additive inhibitory effect on the insulin response when combined with PACAP-(6—27). The PACAP antagonism was specific because intravenous PACAP-(6—27) inhibited the insulin response to intravenous PACAP-27 plus glucose without affecting the insulin response to intravenous glucose alone (1 g/kg) or glucose together with other insulin secretagogues of potential incretin relevance of intestinal (GLP-1, gastric inhibitory polypeptide, cholecystokinin) and neural (vasoactive intestinal peptide, gastrin-releasing peptide, cholinergic agonism) origin. We conclude that PACAP contributes to the insulin response to gastric glucose in mice and suggest that PACAP is involved in the regulation of prandial insulin secretion.

The Effect of Zinc-Crystallized Glucagon-Like Peptide-1 on Insulin Secretion of Macroencapsulated Pancreatic Islets

2001 ◽  
Vol 7 (1) ◽  
pp. 35-44 ◽  
Author(s):  
Heather Gappa ◽  
Miroslav Baudyš ◽  
Jae Joon Koh ◽  
Sung Wan Kim ◽  
You Han Bae
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

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.

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