Insulin secretion and plasma levels of glucose-dependent insulinotropic peptide and glucagon-like peptide 1 67?36 amide9 after oral glucose in cirrhosis*1

OBJECTIVE: The gastrointestinal hormones, gastric inhibitory polypeptide (GIP) and glucagon-like peptide 1 (GLP-1), are both released from the gut after oral glucose ingestion and stimulate insulin secretion. This study examined the release of these hormones in subjects with impaired glucose tolerance (IGT), which precedes the development of non-insulin-dependent diabetes. DESIGN AND METHODS: Six postmenopausal women with IGT, aged 59 years, underwent a 75 g oral glucose tolerance test and plasma levels of GIP and GLP-1 were determined regularly during the following 2 h. The results were compared with those in seven age- and weight-matched women with normal glucose tolerance (NGT). RESULTS: Basal plasma levels of GIP and GLP-1 were not different between the groups. In response to the oral glucose ingestion, plasma levels of both GIP and GLP-1 increased in both groups. The plasma GIP increase after glucose ingestion was, however, reduced in women with IGT. Thus, the GIP response as determined as the area under the curve for the 60 min after oral glucose was 34.8 +/- 3.2 pmol/l per min in women with IGT versus 56.4 +/- 7.8 pmol/l per min in those with NGT (P = 0.021). In contrast, the GLP-1 response to oral glucose was not different between the groups. By definition, the glucose response to oral glucose was markedly increased in women with IGT, and the insulin response during the second hour after glucose ingestion was exaggerated. CONCLUSIONS: The GIP response to oral glucose is impaired in postmenopausal women with IGT, whereas the plasma GLP-1 response is not affected.

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TNF signaling impacts glucagon-like peptide-1 expression and secretion

Journal of Molecular Endocrinology ◽

10.1530/jme-18-0129 ◽

2018 ◽

Vol 61 (4) ◽

pp. 153-161 ◽

Cited By ~ 2

Author(s):

Sufang Chen ◽

Wei Wei ◽

Minjie Chen ◽

Xiaobo Qin ◽

Lianglin Qiu ◽

...

Keyword(s):

Insulin Secretion ◽

Glucose Metabolism ◽

Glucose Tolerance ◽

Glucose Tolerance Test ◽

Tolerance Test ◽

Oral Glucose ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Deficient Mice

Numerous studies have implicated tumor necrosis factor α (TNFα) in the pathogenesis of type 2 diabetes. However, the role of its primary receptor, TNF receptor 1 (TNFR1), in homeostatic regulation of glucose metabolism is still controversial. In addition to TNFα, lymphotoxin α (LTα) binds to and activates TNFR1. Thus, TNFα and LTα together are known as TNF. To delineate the role of TNF signaling in glucose homeostasis, the present study ascertained how TNF signaling deficiency affects major regulatory components of glucose homeostasis. To this end, normal diet-fed male TNFR1-deficient mice (TNFR1−/−), TNFα/LTα/LTβ triple-deficient mice (TNF/LT∆3) and their littermate controls were subjected to intraperitoneal glucose tolerance test, insulin tolerance test and oral glucose tolerance test. The present results showed that TNFR1−/− and TNF/LT∆3 mice vs their controls had comparable body weight, tolerance to intraperitoneal glucose and sensitivity to insulin. However, their tolerance to oral glucose was significantly increased. Additionally, glucose-induced insulin secretion assessments revealed that TNFR1 or TNF/LT deficiency significantly increased oral but not intraperitoneal glucose-induced insulin secretion. Consistently, qPCR and immunohistochemistry analyses showed that TNFR1−/− and TNF/LT∆3 mice vs their controls had significantly increased ileal expression of glucagon-like peptide-1 (GLP-1), one of the primary incretins. Their oral glucose-induced secretion of GLP-1 was also significantly increased. These data collectively suggest that physiological TNF signaling regulates glucose metabolism primarily through effects on GLP-1 expression and secretion and subsequently insulin secretion.

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RANTES (CCL5) reduces glucose-dependent secretion of glucagon-like peptides 1 and 2 and impairs glucose-induced insulin secretion in mice

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00329.2013 ◽

2014 ◽

Vol 307 (3) ◽

pp. G330-G337 ◽

Cited By ~ 10

Author(s):

Ramona Pais ◽

Tamara Zietek ◽

Hans Hauner ◽

Hannelore Daniel ◽

Thomas Skurk

Keyword(s):

Insulin Secretion ◽

Glucose Transporter ◽

Cell Loss ◽

Oral Glucose ◽

Diabetes Therapy ◽

Incretin Hormone ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Type 2 diabetes is associated with elevated circulating levels of the chemokine RANTES and with decreased plasma levels of the incretin hormone glucagon-like peptide 1 (GLP-1). GLP-1 is a peptide secreted from intestinal L-cells upon nutrient ingestion. It enhances insulin secretion from pancreatic β-cells and protects from β-cell loss but also promotes satiety and weight loss. In search of chemokines that may reduce GLP-1 secretion we identified RANTES and show that it reduces glucose-stimulated GLP-1 secretion in the human enteroendocrine cell line NCI-H716, blocked by the antagonist Met-RANTES, and in vivo in mice. RANTES exposure to mouse intestinal tissues lowers transport function of the intestinal glucose transporter SGLT1, and administration in mice reduces plasma GLP-1 and GLP-2 levels after an oral glucose load and thereby impairs insulin secretion. These data show that RANTES is involved in altered secretion of glucagon-like peptide hormones most probably acting through SGLT1, and our study identifies the RANTES-receptor CCR1 as a potential target in diabetes therapy.

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Role of a Dual Glucose-Dependent Insulinotropic Peptide (GIP)/Glucagon-like Peptide-1 Receptor Agonist (Twincretin) in Glycemic Control: From Pathophysiology to Treatment

Life ◽

10.3390/life12010029 ◽

2021 ◽

Vol 12 (1) ◽

pp. 29

Author(s):

Maria Chiara Pelle ◽

Michele Provenzano ◽

Isabella Zaffina ◽

Roberta Pujia ◽

Federica Giofrè ◽

...

Keyword(s):

Clinical Trials ◽

Insulin Secretion ◽

Phase 1 ◽

Synergetic Effect ◽

Insulin Response ◽

Gut Hormones ◽

Acute Effect ◽

Oral Glucose ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are two gut hormones, defined incretins, responsible for the amplification of insulin secretion after oral glucose intake. Unlike GLP-1, GIP has little acute effect on insulin secretion and no effect on food intake; instead it seems that the GIP may be an obesity-promoting hormone. In patients with type2 diabetes mellitus (T2DM) some studies found a downregulation of GIP receptors on pancreatic β cells caused by hyperglycemic state, but the glucagonotropic effect persisted. Agonists of the receptor for the GLP-1 have proven successful for the treatment of diabetes, since they reduce the risk for cardiovascular and renal events, but the possible application of GIP as therapy for T2DM is discussed. Moreover, the latest evidence showed a synergetic effect when GIP was combined with GLP-1 in monomolecular co-agonists. In fact, compared with the separate infusion of each hormone, the combination increased both insulin response and glucagonostatic response. In accordance with theseconsiderations, a dual GIP/GLP-1receptor agonist, i.e., Tirzepatide, known as a “twincretin” had been developed. In the pre-clinical trials, as well as Phase 1–3 clinical trials, Tirzepatideshowedpotent glucose lowering and weight loss effects within an acceptable safety.

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The Impact of a Large Bolus Dose of l-leucine and l-isoleucine on Enteroendocrine and Pancreatic Hormones, and Glycemia in Healthy, Inactive Adults

Nutrients ◽

10.3390/nu11112650 ◽

2019 ◽

Vol 11 (11) ◽

pp. 2650 ◽

Cited By ~ 1

Author(s):

Daniel E. Newmire ◽

Eric Rivas ◽

Sarah E. Deemer ◽

Darryn S. Willoughby ◽

Victor Ben-Ezra

Keyword(s):

Bolus Dose ◽

Glucose Tolerance Test ◽

Area Under The Curve ◽

Tolerance Test ◽

Oral Glucose ◽

Pancreatic Hormones ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Insulinotropic Peptide ◽

The Impact

Background: The ingestion of whey protein and amino acids with carbohydrate (CHO) enhances the release of glucagon-like peptide-1 (GLP-1) and glucose-dependent-insulinotropic peptide (GIP) that promote insulin secretion. It is unknown if L-isoleucine (Ile) and L-leucine (Leu) have this same effect. The purpose of this study was to examine how Ile and Leu influence both GLP-1 and GIP, subsequent pancreatic hormones, and glycemia in healthy, inactive adults. Methods: Twelve adults (6F/6M; age 27.4 ± 2 years; BMI 26.3 ± 2 kg/m2; lean body mass 53.2 ± 5 kg; body fat 34.1 ± 3%) completed four conditions in a randomized, cross-over fashion. Treatments standardized (0.3 g/kg·LBM−1) (1) Leu, (2) Ile, (3) Equal (1:1 g) of Leu + Ile, and (4) placebo (Pla, 3.5 g inert stevia) ingested 30 min prior to an oral glucose tolerance test (OGTT). Samples of plasma glucose, insulin, glucagon, GIPTotal, and GLP-1Active were assessed. Results: A treatment (p = 0.01) effect comparing Ile vs. Leu (p = 0.02) in GIPTotal. Area under the curve showed an increase in GIPTotal from Ile compared to Leu and Pla (p = 0.03). No effect was found on GLP-1. The ingestion of Ile prior to CHO augmented GIP concentration greater than Leu or Pla. No correlation was found between GIP, insulin, and glucose between conditions. Conclusions: Ile impacts GIP concentration, which did not relate to either insulin or glucose concentrations. Neither Ile, nor Leu seem to have an effect on hyperglycemia ingested prior to a CHO drink.

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