scholarly journals The role of incretins on insulin function and glucose homeostasis

Endocrinology ◽  
2021 ◽  
Author(s):  
Jens Juul Holst ◽  
Lærke Smidt Gasbjerg ◽  
Mette Marie Rosenkilde
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Postprandial Glucose ◽  
Normal Glucose Tolerance ◽  
Incretin Effect ◽  
Normal Glucose ◽  
Individual Contributions ◽  
Glucagon Like Peptide 1 ◽  
The Individual

Abstract The incretin effect – the amplification of insulin secretion after oral versus intravenous administration of glucose as a mean to improve glucose tolerance – was suspected even before insulin was discovered, and today we know that the effect is due to the secretion of two insulinotropic peptides, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). But how important is it? Physiological experiments have shown that, because of the incretin effect, we can ingest increasing amounts of amounts of glucose (carbohydrates) without increasing postprandial glucose excursions, which otherwise might have severe consequences. The mechanism behind this is incretin-stimulated insulin secretion. The availability of antagonists for GLP-1 and most recently also for GIP has made it possible to directly estimate the individual contributions to postprandial insulin secretion of a) glucose itself: 26%; b) GIP: 45%; and c) GLP-1: 29%. Thus, in healthy individuals, GIP is the champion. When the action of both incretins is prevented, glucose tolerance is pathologically impaired. Thus, after 100 years of research, we now know that insulinotropic hormones from the gut are indispensable for normal glucose tolerance. The loss of the incretin effect in type 2 diabetes, therefore, contributes greatly to the impaired postprandial glucose control.

scholarly journals Regional Variations of Insulin Secretion and Insulin Sensitivity in Japanese Participants With Normal Glucose Tolerance

2021 ◽  
Vol 8 ◽  
Author(s):  
Kiriko Watanabe ◽  
Moritake Higa ◽  
Yoshimasa Hasegawa ◽  
Akihiro Kudo ◽  
Richard C. Allsopp ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Regional Differences ◽  
Insulin Response ◽  
Normal Glucose Tolerance ◽  
Sensitivity Index ◽  
Insulinogenic Index ◽  
Genetic Traits ◽  
Normal Glucose

Purpose: Regional differences in dietary patterns in Asian countries might affect the balance of insulin response and sensitivity. However, this notion is yet to be validated. To clarify the regional differences in the insulin response and sensitivity and their relationship to nutrients, we compared the insulin secretory response during an oral glucose tolerance test in Japanese participants.Methods: This observational retrospective cohort study analyzed the data from participants with normal glucose tolerance (NGT) from four distinct areas of Japan with regard to the food environment: Fukushima, Nagano, Tokushima, and Okinawa based on data available in the Japanese National Health Insurance database.Results: Although the glucose levels were comparable among the four regions, the insulin responses were significantly different among the regions. This difference was observed even within the same BMI category. The plot between the insulin sensitivity index (Matsuda index) and insulinAUC/glucoseAUC or the insulinogenic index showed hyperbolic relationships with variations in regions. The indices of insulin secretion correlated positively with fat intake and negatively with the intake of fish, carbohydrate calories, and dietary fiber.Conclusions: We found that significant regional differences in insulin response and insulin sensitivity in Japanese participants and that nutritional factors may be linked to these differences independently of body size/adiposity. Insulin response and insulin sensitivity can vary among adult individuals, even within the same race and the same country, and are likely affected by environmental/lifestyle factors as well as genetic traits.

scholarly journals Glucose-Induced Insulin Secretion in Dyslipidemic and Normolipidemic Patients With Normal Glucose Tolerance

Diabetes Care ◽  
2005 ◽  
Vol 28 (5) ◽  
pp. 1225-1227 ◽  
Author(s):  
C. Binnert ◽  
M. Genoud ◽  
G. Seematter ◽  
A. Fekirini ◽  
V. Mooser ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Normal Glucose Tolerance ◽  
Normal Glucose

scholarly journals Disallowance ofAcot7in β-Cells Is Required for Normal Glucose Tolerance and Insulin Secretion

Diabetes ◽  
2016 ◽  
Vol 65 (5) ◽  
pp. 1268-1282 ◽  
Author(s):  
Aida Martinez-Sanchez ◽  
Timothy J. Pullen ◽  
Pauline Chabosseau ◽  
Qifeng Zhang ◽  
Elizabeth Haythorne ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Normal Glucose Tolerance ◽  
Β Cells ◽  
Normal Glucose

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

2018 ◽  
Vol 61 (4) ◽  
pp. 153-161 ◽  
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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