Effects of GLP-1 on Islet Hormone Secretion: Experimental Studies

1997 ◽  
pp. 105-131
Author(s):  
Hans Christoph Fehmann
Keyword(s):  
Hormone Secretion ◽  
Experimental Studies ◽  
Islet Hormone

Chronic effects of caerulein and secretin on the endocrine pancreas of the rat

1983 ◽  
Vol 244 (5) ◽  
pp. G541-G545
Author(s):  
T. Yamada ◽  
J. Brunstedt ◽  
T. Solomon
Keyword(s):  
Dna Content ◽  
Endocrine Pancreas ◽  
Hormone Secretion ◽  
Hormone Synthesis ◽  
Chronic Effects ◽  
Islet Hormone ◽  
Hormone Responses ◽  
Insulin Responses ◽  
Isolated Rat

Secretin and caerulein increase pancreatic somatostatin content when administered chronically to rats. We examined whether this change occurs in vitro and results in altered islet hormone secretion. Pancreatic somatostatin content was increased from 0.25 +/- 0.01 (mean +/- SE) to 0.41 +/- 0.03 nmol/pancreas (P less than 0.001, n = 8) in rats treated for 10 days with caerulein (1 microgram/kg) and secretin (100 micrograms/kg) every 8 h. Somatostatin content in isolated rat pancreatic islets cultured for 10 days in medium containing caerulein and secretin (10(-9) M) was also increased (2.5 +/- 1.0 to 3.6 +/- 1.3 fmol/islet, P less than 0.02, n = 7), although islet DNA content was unchanged. Small increases in glucagon content were observed in both systems, but insulin content was not changed. Isolated perfused pancreases from peptide-treated rats and islets cultured in medium containing the two peptides exhibited significantly greater somatostatin responses to 5 mM glucose and 20 mM theophylline. Insulin responses to glucose and theophylline stimulation were not altered, although basal accumulation of insulin was greater in islet cultures with added caerulein and secretin. These results suggest that caerulein and secretin have direct actions on islet hormone synthesis with effects on hormone responses to stimulation.

Nonadrenergic sympathetic neural influences on basal pancreatic hormone secretion

1988 ◽  
Vol 255 (6) ◽  
pp. E785-E792 ◽  
Author(s):  
B. E. Dunning ◽  
B. Ahren ◽  
R. C. Veith ◽  
G. J. Taborsky
Keyword(s):  
Hormone Secretion ◽  
Immunoreactive Insulin ◽  
High Dose ◽  
Adrenergic Blockade ◽  
Islet Hormone ◽  
Anesthetized Dogs ◽  
Adrenergic Antagonists ◽  
Induced Changes ◽  
Pancreatic Hormone ◽  
Neural Influences

Evidence for peptidergic innervation of the islets of Langerhans is increasing, yet the role of neuropeptides in mediating neurally induced changes of islet function is not clear. To determine if nonadrenergic transmitters make an important contribution to sympathetic neural effects on basal pancreatic hormone secretion, we examined the effect of local sympathetic nerve stimulation (SNS) on the output of immunoreactive insulin (IRI), immunoreactive glucagon (IRG), and somatostatin (SLI) from the duodenal lobe of the pancreas in situ in halothane-anesthetized dogs, under conditions where the actions of the classical transmitter norepinephrine (NE) should be blocked by propranolol (PROP) and yohimbine (YO). In the absence of adrenergic antagonists, SNS rapidly reduced the output of IRI (delta = -1.34 +/- 0.91 mU/min) and SLI (delta = -600 +/- 350 fmol/min) and stimulated that of IRG (delta = +1.39 +/- 0.57 ng/min). In the presence of PROP and YO, SNS induced similar changes of hormone secretion: delta IRI, -1.30 +/- 0.53 mU/min; delta SLI, -480 +/- 180 fmol/min; delta IRG = +1.89 +/- 0.63 ng/min. Because PROP and YO abolished the pancreatic effects of high dose infusions of NE (1 microgram.kg-1.min-1 iv), we suggest that the antagonists produced sufficient, combined adrenergic blockade at the level of the islet, and we conclude that a nonadrenergic neurotransmitter or modulator plays a major role in mediating sympathetic neural effects on basal islet hormone secretion.

Incretin and islet hormonal responses to fat and protein ingestion in healthy men

2008 ◽  
Vol 295 (4) ◽  
pp. E779-E784 ◽  
Author(s):  
Richard D. Carr ◽  
Marianne O. Larsen ◽  
Maria Sörhede Winzell ◽  
Katarina Jelic ◽  
Ola Lindgren ◽  
...  
Keyword(s):  
Hormone Secretion ◽  
Plain Water ◽  
Islet Function ◽  
Carbohydrate Ingestion ◽  
Healthy Men ◽  
Dipeptidyl Peptidase 4 ◽  
Water Ingestion ◽  
Islet Hormones ◽  
Protein Ingestion ◽  
Islet Hormone

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) regulate islet function after carbohydrate ingestion. Whether incretin hormones are of importance for islet function after ingestion of noncarbohydrate macronutrients is not known. This study therefore examined integrated incretin and islet hormone responses to ingestion of pure fat (oleic acid; 0.88 g/kg) or protein (milk and egg protein; 2 g/kg) over 5 h in healthy men, aged 20–25 yr ( n = 12); plain water ingestion served as control. Both intact (active) and total GLP-1 and GIP levels were determined as was plasma activity of dipeptidyl peptidase-4 (DPP-4). Following water ingestion, glucose, insulin, glucagon, GLP-1, and GIP levels and DPP-4 activity were stable during the 5-h study period. Both fat and protein ingestion increased insulin, glucagon, GIP, and GLP-1 levels without affecting glucose levels or DPP-4 activity. The GLP-1 responses were similar after protein and fat, whereas the early (30 min) GIP response was higher after protein than after fat ingestion ( P < 0.001). This was associated with sevenfold higher insulin and glucagon responses compared with fat ingestion (both P < 0.001). After protein, the early GIP, but not GLP-1, responses correlated to insulin ( r2= 0.86; P = 0.0001) but not glucagon responses. In contrast, after fat ingestion, GLP-1 and GIP did not correlate to islet hormones. We conclude that, whereas protein and fat release both incretin and islet hormones, the early GIP secretion after protein ingestion may be of primary importance to islet hormone secretion.

scholarly journals Meal feeding improves oral glucose tolerance in male rats and causes adaptations in postprandial islet hormone secretion that are independent of plasma incretins or glycemia

2014 ◽  
Vol 307 (9) ◽  
pp. E784-E792 ◽  
Author(s):  
Torsten P. ◽  
Benedikt A. Aulinger ◽  
Eric P. Smith ◽  
Deborah L. Drazen ◽  
Yve Ulrich-Lai ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Hormone Secretion ◽  
Insulin Response ◽  
Male Rats ◽  
Oral Glucose ◽  
Light Cycle ◽  
Oral Glucose Tolerance ◽  
Islet Hormone

Meal-fed (MF) rats with access to food for only 4 consecutive hours during the light cycle learn to eat large meals to maintain energy balance. MF animals develop behavioral and endocrine changes that permit glucose tolerance despite increased meal size. We hypothesized that enhanced activity of the enteroinsular axis mediates glucose homeostasis during MF. Cohorts of rats were allocated to MF or ad libitum (AL) regimens for 2–4 wk. Insulin secretion and glucose tolerance were determined after oral carbohydrate and intraperitoneal (ip) and intravenous (iv) glucose. MF rats ate less than AL in the first week but maintained a comparable weight trajectory thereafter. MF rats had decreased glucose excursions after a liquid mixed meal (AUC: MF 75 ± 7, AL 461 ± 28 mmol·l−1·min, P < 0.001), with left-shifted insulin secretion (AUC0–15: MF 31.0 ± 4.9, AL 9.6 ± 4.4 pM·min, P < 0.02), which peaked before a significant rise in blood glucose. Both groups had comparable fasting glucagon levels, but postprandial responses were lower with MF. However, neither intestinal expression of proGIP and proglucagon mRNA nor plasma incretin levels differed between MF and AL groups. There were no differences in the insulin response to ip or iv glucose between MF and AL rats. These findings demonstrate that MF improves oral glucose tolerance and is associated with significant changes in postprandial islet hormone secretion. Because MF enhanced β-cell function during oral but not parenteral carbohydrate administration, and was not accounted for by changes in circulating incretins, these results support a neural mechanism of adaptive insulin secretion.

Intra-islet regulation of hormone secretion by glucagon-like peptide-1-(7--36) amide

1995 ◽  
Vol 269 (6) ◽  
pp. G852-G860 ◽  
Author(s):  
R. S. Heller ◽  
G. W. Aponte
Keyword(s):  
Monoclonal Antibodies ◽  
Insulin Secretion ◽  
Hormone Secretion ◽  
Glucagon Secretion ◽  
Posttranslational Processing ◽  
Alpha Cells ◽  
Islet Hormone ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Peptide Product

Glucagon-like peptide (GLP)-1-(7--36) amide, a peptide product of the posttranslational processing of pancreatic and intestinal proglucagon, has been shown to regulate insulin secretion. Monoclonal antibodies to glucagon and GLP-1-(7--36) amide were generated to localize GLP-1-(7--36) amide in the pancreatic islets by immunocytochemistry and radioimmunoassay. GLP-1-(7--36) amide immunoreactivity was found in some, but not all, glucagon-containing alpha-cells. Displaceable receptor binding for GLP-1-(7--36) amide and nonamidated GLP-1-(7--37) on hormone secretion were investigated using isolated pancreatic islet preparations. GLP-1-(7--37) and -(7--36) amide significantly increased insulin and somatostatin release in the concentration range of 0.01-100 nM in 11.0 mM glucose. GLP-1-(7--37) and -(7--36) amide had no effect on glucagon secretion in the presence of 11.0 mM glucose. GLP-1-(7--36) amide was released from isolated islets in response to 2.25, 5.5, and 11.0 mM glucose. These results suggest that pancreatic GLP-1 may be important in the regulation of intra-islet hormone secretion.

Characterization of growth hormone-releasing hormone stimulation of the endocrine pancreas: Studies with α- and β-adrenergic and cholinergic antagonists

1987 ◽  
Vol 114 (4) ◽  
pp. 589-594 ◽  
Author(s):  
K. Hermansen ◽  
A. M. Kappelgaard
Keyword(s):  
Growth Hormone ◽  
Hormone Receptors ◽  
Islet Cells ◽  
Hormone Secretion ◽  
Cholinergic Receptor ◽  
Cholinergic Antagonists ◽  
Growth Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Islet Hormone ◽  
Stimulation Of

Abstract. The 40 aminoacids residue of pancreatic growth hormone-releasing hormone stimulates the secretion of insulin, glucagon, an somatostatin from the pancreas. To determine whether this stimulation of islet hormone secretion is mediated via adrenergic or cholinergic receptor sites, we studied the effects of 30 nmol/l of the growth hormone-releasing hormone on the release of insulin, glucagon, and somatostatin in the presence of either α-adrenergic (phentolamine), β-adrenergic (propranolol) or cholinergic (atropine) blocking agents. The responses to the growth hormonereleasing hormone were not significantly modified by adrenergic or cholinergic blockers. The findings rule out an interaction with adrenergic and cholinergic receptors on islet cells. It is at present unknown whether the growth hormone-releasing hormone stimulates islet hormone secretion via an interaction with specific growth hormone-releasing hormone receptors or vasoactive intestinal peptide receptors.

scholarly journals Gastric bypass alters both glucose-dependent and glucose-independent regulation of islet hormone secretion

Obesity ◽  
2015 ◽  
Vol 23 (10) ◽  
pp. 2046-2052 ◽  
Author(s):  
Marzieh Salehi ◽  
Stephen C. Woods ◽  
David A. D'Alessio
Keyword(s):  
Gastric Bypass ◽  
Hormone Secretion ◽  
Islet Hormone

scholarly journals Islet Health, Hormone Secretion, and Insulin Responsivity with Low-Carbohydrate Feeding in Diabetes

Metabolites ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 455
Author(s):  
Cassandra A. A. Locatelli ◽  
Erin E. Mulvihill
Keyword(s):  
Ketone Bodies ◽  
Hormone Secretion ◽  
Diabetes Research ◽  
Carbohydrate Restriction ◽  
Carbohydrate Feeding ◽  
Low Carbohydrate ◽  
Islet Hormone ◽  
The Usa ◽  
Preclinical And Clinical Studies

Exploring new avenues to control daily fluctuations in glycemia has been a central theme for diabetes research since the Diabetes Control and Complications Trial (DCCT). Carbohydrate restriction has re-emerged as a means to control type 2 diabetes mellitus (T2DM), becoming increasingly popular and supported by national diabetes associations in Canada, Australia, the USA, and Europe. This approval comes from many positive outcomes on HbA1c in human studies; yet mechanisms underlying their success have not been fully elucidated. In this review, we discuss the preclinical and clinical studies investigating the role of carbohydrate restriction and physiological elevations in ketone bodies directly on pancreatic islet health, islet hormone secretion, and insulin sensitivity. Included studies have clearly outlined diet compositions, including a diet with 30% or less of calories from carbohydrates.

198-OR: Role for the Cationic Amino Acid Transporter Slc7a2 in Alpha-Cell Proliferation and Islet Hormone Secretion

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 198-OR
Author(s):  
ERICK SPEARS ◽  
MATTHEW SHOU ◽  
WALTER A. SIV ◽  
CHUNHUA DAI ◽  
WENBIAO CHEN ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Amino Acid ◽  
Hormone Secretion ◽  
Amino Acid Transporter ◽  
Alpha Cell ◽  
Cationic Amino Acid Transporter ◽  
Cationic Amino Acid ◽  
Islet Hormone ◽  
Acid Transporter
Sign in / Sign up

Export Citation Format

Share Document