Calcitonin modulation of insulin and glucagon secretion in man

1982 ◽  
Vol 242 (3) ◽  
pp. E206-E213 ◽  
Author(s):  
D. Giugliano ◽  
N. Passariello ◽  
S. Sgambato ◽  
R. Torella ◽  
F. D'Onofrio
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Insulin Response ◽  
Glucagon Secretion ◽  
Suppressive Effect ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Acute Insulin Response ◽  
Insulin Responses ◽  
Effect Of Glucose

These studies were undertaken to evaluate the effect of different doses of calcitonin on insulin and glucagon responses to intravenous glucase loads and to assess the mechanism/s by which calcitonin inhibits insulin secretion in man. In our studies, even the infusion of the 1-U dose of calcitonin was found to inhibit by 45% the acute insulin response to a glucose (20 g) pulse. This effect was associated with a significant decrease in glucose disappearance rates. These negative effects of calcitonin on both insulin secretion and glucose tolerance were dose-related. The inhibition of the acute insulin response to glucose was 65% and up to 90% with the infusion of the 4- and 8-U doses, respectively. The suppressive effect of glucose on glucagon secretion was significantly reduced by calcitonin. The inhibitory effect of calcitonin on insulin responses to glucose (5 g) and glucose tolerance was reversed by both theophylline and calcium. By contrast, infusion of lysine acetylsalicylate to block the synthesis of endogenous prostaglandins did not diminish the inhibitory effect of calcitonin on insulin secretion. These results demonstrate that a) calcitonin inhibits glucose-induced insulin responses and deteriorates glucose tolerance in normal humans in a dose-dependent manner; b) calcitonin reduces the suppressive effect of glucose on glucagon secretion in a dose-related fashion; and c) both theophylline and calcium reverse the inhibitory effect of calcitonin on insulin secretion. It is hypothesized that calcitonin effects on insulin and glucagon release are mediated via a change in calcium redistribution in the islet cells.

Theophylline prevents the inhibitory effect of prostaglandin E 2 on glucose-induced insulin secretion in man

1988 ◽  
Vol 118 (2) ◽  
pp. 187-192 ◽  
Author(s):  
D. Giugliano ◽  
D. Cozzolino ◽  
T. Salvatore ◽  
R. Giunta ◽  
R. Torella
Keyword(s):  
Insulin Secretion ◽  
Inhibitory Action ◽  
Insulin Response ◽  
Inhibitory Effect ◽  
Prostaglandin E ◽  
Intracellular Camp ◽  
Adenylate Cyclase System ◽  
Loading Dose ◽  
Phosphodiesterase Activity ◽  
Acute Insulin Response

Abstract. This study was undertaken to assess the mechanism by which prostaglandins of the E series inhibit glucose-induced insulin secretion in man. Acute insulin response (mean change 3–10 min) to iv glucose (0.33 g/kg) was decreased by 40% during the infusion of prostaglandin E2 (10 μg/min) and glucose disappearance rates were reduced (P < 0.05). Insulin response to arginine (5 g iv) and tolbutamide (1 g iv) were not affected by the same rate of prostaglandin E2 infusion. The inhibitory effect of prostaglandin E2 on glucoseinduced insulin secretion was prevented by theophylline (100 mg as a loading dose followed by a 5 mg/min infusion), a drug that increases the intracellular cAMP concentrations by inhibiting phosphodiesterase activity. Our data suggest the involvement of the adenylate cyclase system in the inhibitory action of prostaglandin E2 on glucose-induced insulin secretion in man.

scholarly journals The stimulation of insulin secretion by d-glyceraldehyde correlates with its rate of oxidation in islet cells

1995 ◽  
Vol 310 (1) ◽  
pp. 215-220 ◽  
Author(s):  
O Alcázar ◽  
E Giné ◽  
Z Qiu-Yue ◽  
J Tamarit-Rodríguez
Keyword(s):  
Insulin Secretion ◽  
Islet Cells ◽  
Aerobic Glycolysis ◽  
Metabolic Effects ◽  
Dependent Manner ◽  
Alternative Routes ◽  
Insulin Responses ◽  
Effect Of Glucose ◽  
Dose Dependent ◽  
Lower Capacity

D-Glyceraldehyde's capacity to mimic the effect of D-glucose on insulin secretion has not yet been sufficiently substantiated. It has been recently proposed, however, that they might act through different mechanisms in insulin-secreting tumoral cells. Therefore, we have performed a dose-related study of both the secretory and metabolic effects of D-glyceraldehyde on islets, which have been compared with those produced by D-glucose. D-Glyceraldehyde's capacity to stimulate secretion was paralleled in a dose-dependent manner by its rate of oxidation to 14CO2. Partial inhibition of D-glyceraldehyde oxidation by beta-iodoacetamide resulted in a proportional decrease in the secretory response. L-Glyceraldehyde, which was apparently very poorly oxidized by islets, did not stimulate secretion. The ratio of the maximum insulin responses D-glyceraldehyde and D-glucose (57%) correlated with the ratio of their respective maximum rates of oxidation (68%). At sub-maximal concentrations there was a potentiation of the secretagogue effects of the hexose by the triose, which was not apparent at a maximum effective dose of glucose. It is concluded that D-glyceraldehyde mimics the secretory effect of glucose because, similarly to the hexose, it is metabolized through islet aerobic glycolysis. The lower potency of D-glyceraldehyde as an insulin secretagogue than D-glucose is determined by the lower capacity of islets to oxidize the triose compared with the hexose. D-Glyceraldehyde, unlike D-glucose, is metabolized in islets to D-lactate. Alternative routes for the metabolism of D-glyceraldehyde might explain some of the secretagogue differences between the triose and the hexose.

scholarly journals γ-Hydroxybutyrate does not mediate glucose inhibition of glucagon secretion

2020 ◽  
Vol 295 (16) ◽  
pp. 5419-5426
Author(s):  
Qian Yu ◽  
Bao Khanh Lai ◽  
Parvin Ahooghalandari ◽  
Anders Helander ◽  
Erik Gylfe ◽  
...  
Keyword(s):  
Glucagon Secretion ◽  
Suppressive Effect ◽  
Inhibitory Effect ◽  
Human Islets ◽  
Glucagon Release ◽  
Paracrine Factors ◽  
Glucose Inhibition ◽  
Mouse Islets ◽  
Blood Glucose Concentrations ◽  
Effect Of Glucose

Hypersecretion of glucagon from pancreatic α-cells strongly contributes to diabetic hyperglycemia. Moreover, failure of α-cells to increase glucagon secretion in response to falling blood glucose concentrations compromises the defense against hypoglycemia, a common complication in diabetes therapy. However, the mechanisms underlying glucose regulation of glucagon secretion are poorly understood and likely involve both α-cell–intrinsic and intraislet paracrine signaling. Among paracrine factors, glucose-stimulated release of the GABA metabolite γ-hydroxybutyric acid (GHB) from pancreatic β-cells might mediate glucose suppression of glucagon release via GHB receptors on α-cells. However, the direct effects of GHB on α-cell signaling and glucagon release have not been investigated. Here, we found that GHB (4–10 μm) lacked effects on the cytoplasmic concentrations of the secretion-regulating messengers Ca2+ and cAMP in mouse α-cells. Glucagon secretion from perifused mouse islets was also unaffected by GHB at both 1 and 7 mm glucose. The GHB receptor agonist 3-chloropropanoic acid and the antagonist NCS-382 had no effects on glucagon secretion and did not affect stimulation of secretion induced by a drop in glucose from 7 to 1 mm. Inhibition of endogenous GHB formation with the GABA transaminase inhibitor vigabatrin also failed to influence glucagon secretion at 1 mm glucose and did not prevent the suppressive effect of 7 mm glucose. In human islets, GHB tended to stimulate glucagon secretion at 1 mm glucose, an effect mimicked by 3-chloropropanoic acid. We conclude that GHB does not mediate the inhibitory effect of glucose on glucagon secretion.

scholarly journals Increased insulin secretion and normalization of glucose tolerance by cholinergic agonism in high fat-fed mice

1999 ◽  
Vol 277 (1) ◽  
pp. E93-E102 ◽  
Author(s):  
Bo Ahrén ◽  
Per Sauerberg ◽  
Christian Thomsen
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Insulin Response ◽  
Acute Insulin Response ◽  
High Fat ◽  
Cholinergic Agonist ◽  
Insulin Resistant ◽  
Glucose Stimulated Insulin Secretion ◽  
Improve Glucose Tolerance

Increased insulinotropic activity by the cholinergic agonist carbachol exists in insulin-resistant high fat-fed C57BL/6J mice. We examined the efficiency and potency of carbachol to potentiate glucose-stimulated insulin secretion and to improve glucose tolerance in these animals. Intravenous administration of carbachol (at 15 and 50 nmol/kg) markedly potentiated glucose (1 g/kg)-stimulated insulin secretion in mice fed both a control and a high-fat diet (for 12 wk), with a higher relative potentiation in high fat-fed mice measured as increased (1–5 min) acute insulin response and area under the 50-min insulin curve. Concomitantly, glucose tolerance was improved by carbachol. In fact, carbachol normalized glucose-stimulated insulin secretion and glucose tolerance in mice subjected to a high-fat diet. Carbachol (>100 nmol/l) also potentiated glucose-stimulated insulin secretion from isolated islets with higher efficiency in high fat-fed mice. In contrast, binding of the muscarinic receptor antagonist [ N- methyl-3H]scopolamine to islet muscarinic receptors and the contractile action of carbachol on ileum muscle strips were not different between the two groups. We conclude that carbachol normalizes glucose tolerance in insulin resistance.

scholarly journals Kisspeptin-13 inhibits insulin secretion without affecting glucagon or somatostatin release: study in the perfused rat pancreas

2007 ◽  
Vol 196 (2) ◽  
pp. 283-290 ◽  
Author(s):  
R A Silvestre ◽  
E M Egido ◽  
R Hernández ◽  
J Marco
Keyword(s):  
Insulin Secretion ◽  
Insulin Response ◽  
Human Islets ◽  
Dependent Manner ◽  
Cell Secretion ◽  
Perfused Rat Pancreas ◽  
Rat Pancreas ◽  
D Cell ◽  
Galanin Receptors ◽  
Insulin Responses

Kisspeptins are a family of peptides encoded by the KISS1 gene, which binds to G-protein-coupled receptor (GPR54), an orphan GPR54 related to galanin receptors. Endogenous forms composed of 54, 14, and 13 amino acids have been identified. Kisspeptin and GPR54 mRNAs have been detected in pancreatic B and A cells. Furthermore, kisspeptin-54 has been shown to slightly stimulate the last phase of glucose-induced insulin secretion in mouse and human islets and to inhibit insulin release in MIN6 cells. We have investigated the effect of kisspeptin-13 on insulin, glucagon, and somatostatin secretion. The study was performed in the perfused rat pancreas. Glucose, arginine, carbachol, and exendin-4 were used as secretagogues. Hormones were measured by RIA. Kisspeptin-13 reduced glucose-induced insulin secretion in a dose-dependent manner (IC50=1.2 nM) and inhibited the insulin responses to both carbachol and exendin-4. Kisspeptin-13 blocked arginine-induced insulin secretion without affecting the glucagon or somatostatin responses to this amino acid, thus indicating that kisspeptin-13 influences B cells directly, rather than through an A- or D-cell paracrine effect. The reduction of the insulin response to exendin-4 induced by kisspeptin-13 was also observed in pertussis toxin-treated rats, thus suggesting an inhibition independent of Gi proteins. In view of the potent insulinostatic effect of kisspeptin-13, it is tempting to speculate that kisspeptins may be implicated in the regulation of B-cell secretion.

GLUCOSE TOLERANCE AND INSULIN SECRETION IN HYPERTHYROIDISM

1977 ◽  
Vol 84 (3) ◽  
pp. 576-587 ◽  
Author(s):  
O. Ortved Andersen ◽  
Th. Friis ◽  
B. Ottesen
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Cell Mass ◽  
Insulin Response ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Glucose Response ◽  
Intravenous Glucose ◽  
Insulin Responses

ABSTRACT To evaluate the glucose tolerance and insulin secretion in hyperthyroidism patients were examined in the toxic state and after they had been made euthyroid. Fasting values: In 42 untreated patients the glucose- and insulin concentrations in serum were significantly elevated. In 24 treated patients the glucose concentrations became normal, while the insulin concentrations remained elevated. Oral-glucose-tolerance test: In 20 untreated patients the glucose- and insulin responses were significantly increased. In 8 treated patients the glucose response became normal, while the insulin response remained unchanged. Intravenous-glucose-tolerance test: In 28 untreated patients the K-values were significantly decreased and the insulin response increased. In 23 treated patients the K-values rose significantly, but the insulin response remained unchanged. Intravenous-tolbutamide test: In 41 untreated patients the glucose concentration decreased significantly compared with the controls, and the insulin responses were significantly increased. In 23 treated patients the glucose concentrations decreased even more, while the insulin response remained unchanged. The results indicate enhanced sensitivity or an increase in the mass of β-cells in hyperthyroidism. The glucose tolerance tests point to an increased peripheral insulin resistance. The normalized glucose tolerance and still enhanced insulin secretion during treatment support the assumption, that hyperthyroidism causes an increase in the β-cell mass.

Insulin as a physiological modulator of glucagon secretion

2008 ◽  
Vol 295 (4) ◽  
pp. E751-E761 ◽  
Author(s):  
Pritpal Bansal ◽  
Qinghua Wang
Keyword(s):  
Insulin Secretion ◽  
Blood Glucose ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Glucagon Secretion ◽  
Suppressive Effect ◽  
Inhibitory Effect ◽  
Β Cells ◽  
Receptor System ◽  
Glucose Levels

Glucose homeostasis is regulated primarily by the opposing actions of insulin and glucagon, hormones that are secreted by pancreatic islets from β-cells and α-cells, respectively. Insulin secretion is increased in response to elevated blood glucose to maintain normoglycemia by stimulating glucose transport in muscle and adipocytes and reducing glucose production by inhibiting gluconeogenesis in the liver. Whereas glucagon secretion is suppressed by hyperglycemia, it is stimulated during hypoglycemia, promoting hepatic glucose production and ultimately raising blood glucose levels. Diabetic hyperglycemia occurs as the result of insufficient insulin secretion from the β-cells and/or lack of insulin action due to peripheral insulin resistance. Remarkably, excessive secretion of glucagon from the α-cells is also a major contributor to the development of diabetic hyperglycemia. Insulin is a physiological suppressor of glucagon secretion; however, at the cellular and molecular levels, how intraislet insulin exerts its suppressive effect on the α-cells is not very clear. Although the inhibitory effect of insulin on glucagon gene expression is an important means to regulate glucagon secretion, recent studies suggest that the underlying mechanisms of the intraislet insulin on suppression of glucagon secretion involve the modulation of KATP channel activity and the activation of the GABA-GABAA receptor system. Nevertheless, regulation of glucagon secretion is multifactorial and yet to be fully understood.

scholarly journals 4-Hydroxyisoleucine: experimental evidence of its insulinotropic and antidiabetic properties

1999 ◽  
Vol 277 (4) ◽  
pp. E617-E623 ◽  
Author(s):  
Christophe Broca ◽  
René Gross ◽  
Pierre Petit ◽  
Yves Sauvaire ◽  
Michèle Manteghetti ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Insulin Response ◽  
Oral Glucose ◽  
Dependent Manner ◽  
Insulin Dependent ◽  
Glucose Tolerance Tests ◽  
Insulin Dependent Diabetic ◽  
Single Intravenous Administration

We have recently shown in vitro that 4-hydroxyisoleucine (4-OH-Ile), an amino acid extracted from fenugreek seeds, potentiates insulin secretion in a glucose-dependent manner. The present study was designed to investigate whether 4-OH-Ile could exert in vivo insulinotropic and antidiabetic properties. For this purpose, intravenous or oral glucose tolerance tests (IVGTTs and OGTTs, respectively) were performed not only in normal animals but also in a type II diabetes rat model. During IVGTT in normal rats or OGTT in normal dogs, 4-OH-Ile (18 mg/kg) improved glucose tolerance. The lactonic form of 4-OH-Ile was ineffective in normal rats. In non-insulin-dependent diabetic (NIDD) rats, a single intravenous administration of 4-OH-Ile (50 mg/kg) partially restored glucose-induced insulin response without affecting glucose tolerance; a 6-day subchronic administration of 4-OH-Ile (50 mg/kg, daily) reduced basal hyperglycemia, decreased basal insulinemia, and slightly, but significantly, improved glucose tolerance. In vitro, 4-OH-Ile (200 μM) potentiated glucose (16.7 mM)-induced insulin release from NIDD rat-isolated islets. So, the antidiabetic effects of 4-OH-Ile on NIDD rats result, at least in part, from a direct pancreatic B cell stimulation.

Effects of PACAP1–27 on the canine endocrine pancreas in vivo: interaction with cholinergic mechanism

2003 ◽  
Vol 81 (7) ◽  
pp. 720-729 ◽  
Author(s):  
Nobuharu Yamaguchi ◽  
Tamar Rita Minassian ◽  
Sanae Yamaguchi
Keyword(s):  
Endocrine Pancreas ◽  
Venous Blood ◽  
Insulin Response ◽  
Glucagon Secretion ◽  
Venous Blood Flow ◽  
Dependent Manner ◽  
Cholinergic Mechanism ◽  
Insulin And Glucagon Secretion ◽  
Anesthetized Dogs

The aim of the present study was to characterize the effects of pituitary adenylate cyclase activating polypeptide (PACAP) on the endocrine pancreas in anesthetized dogs. PACAP1–27 and a PACAP receptor (PAC1) blocker, PACAP6–27, were locally administered to the pancreas. PACAP1–27 (0.005–5 μg) increased basal insulin and glucagon secretion in a dose-dependent manner. PACAP6–27 (200 μg) blocked the glucagon response to PACAP1–27 (0.5 μg) by about 80%, while the insulin response remained unchanged. With a higher dose of PACAP6–27 (500 μg), both responses to PACAP1–27 were inhibited by more than 80%. In the presence of atropine with an equivalent dose (128.2 μg) of PACAP6–27 (500 μg) on a molar basis, the insulin response to PACAP1–27 was diminished by about 20%, while the glucagon response was enhanced by about 80%. The PACAP1–27-induced increase in pancreatic venous blood flow was blocked by PACAP6–27 but not by atropine. The study suggests that the endocrine secretagogue effect of PACAP1–27 is primarily mediated by the PAC1 receptor, and that PACAP1–27 may interact with muscarinic receptor function in PACAP-induced insulin and glucagon secretion in the canine pancreas in vivo.Key words: atropine, PACAP, PAC1, muscarinic, interaction.

Effects of Secretin on Insulin Secretion and Glucose Tolerance

1975 ◽  
Vol 53 (6) ◽  
pp. 1115-1121 ◽  
Author(s):  
J. Dupré ◽  
D. J. Chisholm ◽  
T. J. McDonald ◽  
A. Rabinovitch
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Glucose Production ◽  
High Rate ◽  
Immunoreactive Insulin ◽  
Continuous Administration ◽  
Normal Men ◽  
Mean Glucose ◽  
Insulin Responses ◽  
Infusion Period

Effects of intravenous (IV) infusion of secretin during IV infusion of glucose were examined in normal men. Secretin was administered according to three schedules: with each schedule a comparable priming dose was delivered in the first minute, but this was followed by a maintained (120 min) infusion of secretin at a relatively high rate, or by maintained infusion at one-third that rate, or by brief (15 min) infusion at the lower rate. The lower infusion rate produced increments in secretin in the blood within the range attainable during endogenous secretion. By comparison with effects of glucose alone each secretin infusion enhanced the increments of immunoreactive insulin in the blood. Enhancement of the early release (0–5 min) of insulin was similar with each type of secretin infusion, but the integrated changes in insulin levels through the total infusion period were related to the total doses of secretin. With each dose of secretin glucose tolerance was improved but the three mean glucose curves observed during infusions of secretin were not distinguishable from one another in spite of widely different integrated insulin responses. Secretin did not modify suppression of immunoreactive glucagon or free fatty acids in the blood during hyperglycemia. The results suggest that the effect of continuous administration of secretin on glucose tolerance is not simply related to its integrated insulinotropic action. It is suggested that the effect may be highly dependent on enhancement of insulin secretion early in the response to glycemia, or that it may be due to effects of secretin on glucose production or disposal which are not mediated by insulin.

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