scholarly journals Pancreatic polypeptide regulates glucagon release through PPYR1 receptors expressed in mouse and human alpha-cells

2015 ◽  
Vol 1850 (2) ◽  
pp. 343-351 ◽  
Author(s):  
F. Aragón ◽  
M. Karaca ◽  
A. Novials ◽  
R. Maldonado ◽  
P. Maechler ◽  
...  
Keyword(s):  
Pancreatic Polypeptide ◽  
Glucagon Release ◽  
Alpha Cells

scholarly journals The insulinotropic effect of endothelin-1 is mediated by glucagon release from the islet alpha cells

Diabetologia ◽  
1999 ◽  
Vol 42 (11) ◽  
pp. 1302-1307 ◽  
Author(s):  
B. Brock ◽  
S. Gregersen ◽  
K. Kristensen ◽  
J. L. Thomsen ◽  
K. Buschard ◽  
...  
Keyword(s):  
Glucagon Release ◽  
Alpha Cells ◽  
Endothelin 1 ◽  
Insulinotropic Effect

High co-expression of the ghrelin and LEAP2 receptor GHSR with pancreatic polypeptide in mouse and human islets

Endocrinology ◽  
2021 ◽  
Author(s):  
Deepali Gupta ◽  
Georgina K C Dowsett ◽  
Bharath K Mani ◽  
Kripa Shankar ◽  
Sherri Osborne-Lawrence ◽  
...  
Keyword(s):  
Single Cell ◽  
Beta Cells ◽  
Pancreatic Polypeptide ◽  
Alpha Cells ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Ghrelin Receptor ◽  
Cell Clusters ◽  
Delta Cell ◽  
Delta Cells

Abstract Islets represent an important site of direct action of the hormone ghrelin, with expression of the ghrelin receptor (growth hormone secretagogue receptor; GHSR) having been localized variably to alpha-cells, beta-cells, and/or somatostatin (SST)-secreting delta-cells. To our knowledge, GHSR expression by pancreatic polypeptide (PP)-expressing gamma-cells has not been specifically investigated. Here, histochemical analyses of Ghsr-IRES-Cre X Cre-dependent ROSA26-YFP reporter mice showed 85% of GHSR-expressing islet cells co-express PP, 50% co-express SST, and 47% co-express PP + SST. Analysis of single-cell transcriptomic data from mouse pancreas revealed 95% of Ghsr-expressing cells co-express Ppy, 100% co-express Sst, and 95% co-express Ppy + Sst. This expression was restricted to gamma-cell and delta-cell clusters. Analysis of several single-cell human pancreatic transcriptome datasets revealed 59% of GHSR-expressing cells co-express PPY, 95% co-express SST, and 57% co-express PPY + SST. This expression was prominent in delta-cell and beta-cell clusters, also occurring in other clusters including gamma-cells and alpha-cells. GHSR expression levels were upregulated by type 2 diabetes mellitus in beta-cells. In mice, plasma PP positively correlated with fat mass and with plasma levels of the endogenous GHSR antagonist/inverse agonist LEAP2. Plasma PP also elevated upon LEAP2 and synthetic GHSR antagonist administration. These data suggest that in addition to delta-cells, beta-cells, and alpha-cells, PP-expressing pancreatic cells likely represent important direct targets for LEAP2 and/or ghrelin in both mice and humans.

scholarly journals The microRNA-124-iGluR2/3 pathway regulates glucagon release from alpha cells

Oncotarget ◽  
2016 ◽  
Vol 7 (17) ◽  
pp. 24734-24743 ◽  
Author(s):  
Haiyang Zhang ◽  
Rui Liu ◽  
Ting Deng ◽  
Xia Wang ◽  
Hongmei Lang ◽  
...  
Keyword(s):  
Glucagon Release ◽  
Alpha Cells ◽  
Microrna 124

scholarly journals Glucokinase intrinsically regulates glucose sensing and glucagon secretion in pancreatic alpha cells

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Tilo Moede ◽  
Barbara Leibiger ◽  
Pilar Vaca Sanchez ◽  
Elisabetta Daré ◽  
Martin Köhler ◽  
...  
Keyword(s):  
Glucose Sensor ◽  
Glucagon Secretion ◽  
Glucose Sensing ◽  
Glucagon Release ◽  
Alpha Cells ◽  
Intrinsic Factors ◽  
Pancreatic Alpha Cells ◽  
And Function ◽  
Cell Glucose

AbstractThe secretion of glucagon by pancreatic alpha cells is regulated by a number of external and intrinsic factors. While the electrophysiological processes linking a lowering of glucose concentrations to an increased glucagon release are well characterized, the evidence for the identity and function of the glucose sensor is still incomplete. In the present study we aimed to address two unsolved problems: (1) do individual alpha cells have the intrinsic capability to regulate glucagon secretion by glucose, and (2) is glucokinase the alpha cell glucose sensor in this scenario. Single cell RT-PCR was used to confirm that glucokinase is the main glucose-phosphorylating enzyme expressed in rat pancreatic alpha cells. Modulation of glucokinase activity by pharmacological activators and inhibitors led to a lowering or an increase of the glucose threshold of glucagon release from single alpha cells, measured by TIRF microscopy, respectively. Knockdown of glucokinase expression resulted in a loss of glucose control of glucagon secretion. Taken together this study provides evidence for a crucial role of glucokinase in intrinsic glucose regulation of glucagon release in rat alpha cells.

scholarly journals Arginine-vasopressin mediates counter-regulatory glucagon release and is diminished in type 1 diabetes

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Angela Kim ◽  
Jakob G Knudsen ◽  
Joseph C Madara ◽  
Anna Benrick ◽  
Thomas Hill ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Blood Glucose ◽  
Arginine Vasopressin ◽  
Glucagon Secretion ◽  
Glucagon Release ◽  
Alpha Cells ◽  
Major Barrier ◽  
Circulating Levels

Insulin-induced hypoglycemia is a major barrier to the treatment of type-1 diabetes (T1D). Accordingly, it is important that we understand the mechanisms regulating the circulating levels of glucagon - the body's principal blood glucose-elevating hormone which is secreted from alpha-cells of the pancreatic islets. Varying glucose over the range of concentrations that occur physiologically between the fed and fuel-deprived states (from 8 to 4 mM) has no significant effect on glucagon secretion in the perfused mouse pancreas or in isolated mouse islets (in vitro) and yet associates with dramatic changes in plasma glucagon in vivo. The identity of the systemic factor(s) that stimulates glucagon secretion remains unknown. Here, we show that arginine-vasopressin (AVP), secreted from the posterior pituitary, stimulates glucagon secretion. Glucagon-secreting alpha-cells express high levels of the vasopressin 1b receptor gene (Avpr1b). Activation of AVP neurons in vivo increased circulating copeptin (the C-terminal segment of the AVP precursor peptide, a stable surrogate marker of AVP) and increased blood glucose; effects blocked by pharmacological antagonism of either the glucagon receptor or vasopressin 1b receptor. AVP also mediates the stimulatory effects of hypoglycemia produced by exogenous insulin and 2-deoxy-D-glucose on glucagon secretion. We show that the A1/C1 neurons of the medulla oblongata drive AVP neuron activation in response to insulin-induced hypoglycemia. Exogenous injection of AVP in vivo increased cytoplasmic Ca2+ in alpha-cells (implanted into the anterior chamber of the eye) and glucagon release. Hypoglycemia also increases circulating levels of AVP in humans and this hormone stimulates glucagon secretion from isolated human islets. In patients with T1D, hypoglycemia failed to increase both plasma copeptin and glucagon levels. These findings suggest that AVP is a physiological systemic regulator of glucagon secretion and that this mechanism becomes impaired in T1D.

Effects of gastric inhibitory polypeptide, vasoactive intestinal polypeptide and peptide histidine isoleucine on the secretion of hormones by isolated mouse pancreatic islets

1990 ◽  
Vol 125 (3) ◽  
pp. 375-379 ◽  
Author(s):  
C. J. Bailey ◽  
L. C. Wilkes ◽  
J. M. Conlon ◽  
P. H. Armstrong ◽  
K. D. Buchanan
Keyword(s):  
Pancreatic Islets ◽  
Insulin Release ◽  
Vasoactive Intestinal Polypeptide ◽  
Pancreatic Polypeptide ◽  
Glucose Concentration ◽  
Gastric Inhibitory Polypeptide ◽  
Glucagon Release ◽  
Islet Hormones ◽  
Mouse Pancreatic Islets ◽  
Intestinal Polypeptide

ABSTRACT The release of insulin, glucagon, somatostatin and pancreatic polypeptide (PP) by isolated mouse pancreatic islets was determined during 30-min incubations at 5.6 and 16.7 mmol glucose/l in the absence and presence of gastric inhibitory polypeptide (GIP), vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI) at concentrations of 1–1000 nmol/l. Insulin release was enhanced (>50%) by GIP (100–1000 nmol/l) and VIP (1 μmol/l) at 5.6 mmol glucose/l, but not at 16.7 mmol glucose/l. Glucagon release was increased by GIP (100–1000 nmol/l), and by VIP and PHI (1—1000 nmol/l) at both glucose concentrations in a dose-related manner (maximum increases > tenfold). Somatostatin release was similarly increased by GIP (10–1000 nmol/l) at both glucose concentrations. Only the highest concentration (1 μmol/l of PHI tested increased somatostatin release (twofold) at 5.6 mmol glucose/l, whereas PHI and VIP (1–1000 nmol/l reduced (>37%) somatostatin release at 16.7 mmol glucose/l. PP release was increased (49–58%) by 100–1000 nmol GIP/l, but was not significantly altered by VIP, and was reduced (39–56%) by PHI. The results indicate that GIP, VIP and PHI each stimulate glucagon release in a dose-related manner, but they exert discretely different effects on other islet hormones depending upon the dose and the prevailing glucose concentration. Journal of Endocrinology (1990) 125, 375–379

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