Effect of portal glucose sensing on incretin hormone secretion in a canine model

Edgerton, Dale S.; Kraft, Guillaume; Smith, Marta S.; Moore, L. Merkle; Farmer, Ben; Scott, Melanie; Moore, Mary Courtney; Nauck, Michael A.; Cherrington, Alan D.

doi:10.1152/ajpendo.00100.2019

Cited by 9 publications

(2 citation statements)

References 39 publications

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“…Therefore, high concentrations of GIP and GLP‐1 do not cause hypoglycaemia. An incretin effect is observed at similar magnitude in rodents, 10 pigs 11 and in human subjects, 12 but not in dogs 13 . The relative contribution of GIP vs. GLP‐1 secretion and action to the incretin effect may be subject to species differences 14‐17 …”

Section: The Incretin Effect Defines the Main Physiological Role Of Gip And Glp‐1mentioning

confidence: 99%

The evolving story of incretins (GIP and GLP‐1) in metabolic and cardiovascular disease: A pathophysiological update

Nauck

Quast

Wefers

et al. 2021

Diabetes Obesity Metabolism

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202

184

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The incretin hormones glucose‐dependent insulinotropic polypeptide (GIP) and glucagon‐like peptide‐1 (GLP‐1) have their main physiological role in augmenting insulin secretion after their nutrient‐induced secretion from the gut. A functioning entero‐insular (gut‐endocrine pancreas) axis is essential for the maintenance of a normal glucose tolerance. This is exemplified by the incretin effect (greater insulin secretory response to oral as compared to “isoglycaemic” intravenous glucose administration due to the secretion and action of incretin hormones). GIP and GLP‐1 have additive effects on insulin secretion. Local production of GIP and/or GLP‐1 in islet α‐cells (instead of enteroendocrine K and L cells) has been observed, and its significance is still unclear. GLP‐1 suppresses, and GIP increases glucagon secretion, both in a glucose‐dependent manner. GIP plays a greater physiological role as an incretin. In type 2‐diabetic patients, the incretin effect is reduced despite more or less normal secretion of GIP and GLP‐1. While insulinotropic effects of GLP‐1 are only slightly impaired in type 2 diabetes, GIP has lost much of its acute insulinotropic activity in type 2 diabetes, for largely unknown reasons. Besides their role in glucose homoeostasis, the incretin hormones GIP and GLP‐1 have additional biological functions: GLP‐1 at pharmacological concentrations reduces appetite, food intake, and—in the long run—body weight, and a similar role is evolving for GIP, at least in animal studies. Human studies, however, do not confirm these findings. GIP, but not GLP‐1 increases triglyceride storage in white adipose tissue not only through stimulating insulin secretion, but also by interacting with regional blood vessels and GIP receptors. GIP, and to a lesser degree GLP‐1, play a role in bone remodelling. GLP‐1, but not GIP slows gastric emptying, which reduces post‐meal glycaemic increments. For both GIP and GLP‐1, beneficial effects on cardiovascular complications and neurodegenerative central nervous system (CNS) disorders have been observed, pointing to therapeutic potential over and above improving diabetes complications. The recent finding that GIP/GLP‐1 receptor co‐agonists like tirzepatide have superior efficacy compared to selective GLP‐1 receptor agonists with respect to glycaemic control as well as body weight has renewed interest in GIP, which previously was thought to be without any therapeutic potential. One focus of this research is into the long‐term interaction of GIP and GLP‐1 receptor signalling. A GLP‐1 receptor antagonist (exendin [9‐39]) and, more recently, a GIP receptor agonist (GIP [3‐30] NH2) and, hopefully, longer‐acting GIP receptor agonists for human use will be helpful tools to shed light on the open questions. A detailed knowledge of incretin physiology and pathophysiology will be a prerequisite for designing more effective incretin‐based diabetes drugs.

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Section: The Incretin Effect Defines the Main Physiological Role Of Gip And Glp‐1mentioning

confidence: 99%

The evolving story of incretins (GIP and GLP‐1) in metabolic and cardiovascular disease: A pathophysiological update

Nauck

Quast

Wefers

et al. 2021

Diabetes Obesity Metabolism

Self Cite

202

184

View full text Add to dashboard Cite

show abstract

“…This issue is exacerbated at times of rapid changes in glucose. Even with the currently available rapid-acting insulin analogues, the pharmacodynamic response of insulin is impeded by delivery via insulin pumps into the subcutaneous space [ 25 – 27 ]. The hybrid approach adopted for AID systems, in which users need to bolus manually for carbohydrate intake, was developed secondary to these limitations [ 28 ].…”

Section: Limitations Of Aid Systemsmentioning

confidence: 99%

Automated insulin delivery: benefits, challenges, and recommendations. A Consensus Report of the Joint Diabetes Technology Working Group of the European Association for the Study of Diabetes and the American Diabetes Association

Sherr

Heinemann²,

Fleming³

et al. 2022

Diabetologia

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A technological solution for the management of diabetes in people who require intensive insulin therapy has been sought for decades. The last 10 years have seen substantial growth in devices that can be integrated into clinical care. Driven by the availability of reliable systems for continuous glucose monitoring, we have entered an era in which insulin delivery through insulin pumps can be modulated based on sensor glucose data. Over the past few years, regulatory approval of the first automated insulin delivery (AID) systems has been granted, and these systems have been adopted into clinical care. Additionally, a community of people living with type 1 diabetes has created its own systems using a do-it-yourself approach by using products commercialised for independent use. With several AID systems in development, some of which are anticipated to be granted regulatory approval in the near future, the joint Diabetes Technology Working Group of the European Association for the Study of Diabetes and the American Diabetes Association has created this consensus report. We provide a review of the current landscape of AID systems, with a particular focus on their safety. We conclude with a series of recommended targeted actions. This is the fourth in a series of reports issued by this working group. The working group was jointly commissioned by the executives of both organisations to write the first statement on insulin pumps, which was published in 2015. The original authoring group was comprised by three nominated members of the American Diabetes Association and three nominated members of the European Association for the Study of Diabetes. Additional authors have been added to the group to increase diversity and range of expertise. Each organisation has provided a similar internal review process for each manuscript prior to submission for editorial review by the two journals. Harmonisation of editorial and substantial modifications has occurred at both levels. The members of the group have selected the subject of each statement and submitted the selection to both organisations for confirmation.

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2023

Concepts in Biology

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Effect of portal glucose sensing on incretin hormone secretion in a canine model

Cited by 9 publications

References 39 publications

The evolving story of incretins (GIP and GLP‐1) in metabolic and cardiovascular disease: A pathophysiological update

The evolving story of incretins (GIP and GLP‐1) in metabolic and cardiovascular disease: A pathophysiological update

Automated insulin delivery: benefits, challenges, and recommendations. A Consensus Report of the Joint Diabetes Technology Working Group of the European Association for the Study of Diabetes and the American Diabetes Association

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