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 Transformation of postingestive glucose responses after deletion of sweet taste receptor subunits or gastric bypass surgery

2012 ◽  
Vol 303 (4) ◽  
pp. E464-E474 ◽  
Author(s):  
Maartje C. P. Geraedts ◽  
Tatsuyuki Takahashi ◽  
Stephan Vigues ◽  
Michele L. Markwardt ◽  
Andongfac Nkobena ◽  
...  
Keyword(s):  
Gastric Bypass ◽  
Glycemic Control ◽  
Large Intestine ◽  
Molecular Mechanisms ◽  
Hormone Secretion ◽  
Taste Receptor ◽  
Sweet Taste ◽  
Oral Glucose ◽  
Isolated Pancreatic Islets ◽  
Sweet Taste Receptor

The glucose-dependent secretion of the insulinotropic hormone glucagon-like peptide-1 (GLP-1) is a critical step in the regulation of glucose homeostasis. Two molecular mechanisms have separately been suggested as the primary mediator of intestinal glucose-stimulated GLP-1 secretion (GSGS): one is a metabotropic mechanism requiring the sweet taste receptor type 2 (T1R2) + type 3 (T1R3) while the second is a metabolic mechanism requiring ATP-sensitive K+(KATP) channels. By quantifying sugar-stimulated hormone secretion in receptor knockout mice and in rats receiving Roux-en-Y gastric bypass (RYGB), we found that both of these mechanisms contribute to GSGS; however, the mechanisms exhibit different selectivity, regulation, and localization. T1R3−/−mice showed impaired glucose and insulin homeostasis during an oral glucose challenge as well as slowed insulin granule exocytosis from isolated pancreatic islets. Glucose, fructose, and sucralose evoked GLP-1 secretion from T1R3+/+, but not T1R3−/−, ileum explants; this secretion was not mimicked by the KATPchannel blocker glibenclamide. T1R2−/−mice showed normal glycemic control and partial small intestine GSGS, suggesting that T1R3 can mediate GSGS without T1R2. Robust GSGS that was KATPchannel-dependent and glucose-specific emerged in the large intestine of T1R3−/−mice and RYGB rats in association with elevated fecal carbohydrate throughout the distal gut. Our results demonstrate that the small and large intestines utilize distinct mechanisms for GSGS and suggest novel large intestine targets that could mimic the improved glycemic control seen after RYGB.

scholarly journals Customization of biliopancreatic limb length to modulate and sustain antidiabetic effect of gastric bypass surgery

2018 ◽  
Vol 314 (2) ◽  
pp. G287-G299 ◽  
Author(s):  
A. Pal ◽  
D. B. Rhoads ◽  
A. Tavakkoli
Keyword(s):  
Gastric Bypass ◽  
Weight Regain ◽  
Glucose Utilization ◽  
Hormone Secretion ◽  
Limb Length ◽  
Roux Limb ◽  
Dose Response Relationship ◽  
Biliopancreatic Limb ◽  
Relationship Of ◽  
Biliopancreatic Limb Length

Although Roux-en-Y Gastric Bypass (RYGB) remains the most effective treatment for obesity and type 2 diabetes (T2D), many patients fail to achieve remission, or relapse. Increasing intestinal limb lengths of RYGB may improve outcomes, but the mechanistic basis for this remains unclear. We hypothesize biliopancreatic (BP) limb length modulates the antidiabetic effect of RYGB. Rats underwent RYGB with a 20-cm (RYGB-20cm) or 40-cm (RYGB-40cm) BP limb and were compared with control animals. After 2 and 4 wk, portal and systemic blood was sampled during intestinal glucose infusion. Portosystemic gradient was used to calculate intestinal glucose utilization (Gutil), absorption (Gabsorp), and hormone secretion. Intestinal morphology and gene expression were assessed. At 2 wk, Gabsorp progressively decreased with increasing BP limb length; this pattern persisted at 4 wk. Gutil increased ≈70% in both RYGB-20cm and -40cm groups at 2 wk. At 4 wk, Gutil progressively increased with limb length. Furthermore, Roux limb weight, and expression of hexokinase and preproglucagon, exhibited a similar progressive increase. At 4 wk, glucagon-like peptide-1 and -2 levels were higher after RYGB-40cm, with associated increased secretion. We conclude that BP limb length modulates multiple antidiabetic mechanisms, analogous to the dose-response relationship of a drug. Early postoperatively, a longer BP limb reduces Gabsorp. Later, Gutil, Roux limb hypertrophy, hormone secretion, and hormone levels are increased with longer BP limb. Sustained high incretin levels may prevent weight regain and T2D relapse. These data provide the basis for customizing BP limb length according to patient characteristics and desired metabolic effect. NEW & NOTEWORTHY Biliopancreatic limb length in gastric bypass modulates multiple antidiabetic mechanisms, analogous to the dose-response relationship of a drug. With a longer biliopancreatic limb, Roux limb hypertrophy, increased glucose utilization, reduced glucose absorption, and sustained high incretin levels may prevent weight regain and diabetes relapse.

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.

scholarly journals Postprandial Nutrient Handling and Gastrointestinal Hormone Secretion After Roux-en-Y Gastric Bypass vs Sleeve Gastrectomy

2019 ◽  
Vol 156 (6) ◽  
pp. 1627-1641.e1 ◽  
Author(s):  
Maria S. Svane ◽  
Kirstine N. Bojsen-Møller ◽  
Christoffer Martinussen ◽  
Carsten Dirksen ◽  
Jan L. Madsen ◽  
...  
Keyword(s):  
Gastric Bypass ◽  
Sleeve Gastrectomy ◽  
Hormone Secretion ◽  
Gastrointestinal Hormone

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.

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