Effect of 6-week course of glucagon-like peptide 1 on glycaemic control, insulin sensitivity, and β-cell function in type 2 diabetes: a parallel-group study

Zander, Mette; Madsbad, Sten; Madsen, Jakob Torp; Holst, Jens J.

doi:10.1016/s0140-6736(02)07952-7

Cited by 1,188 publications

(940 citation statements)

References 31 publications

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“…Specifically, glucagon-like peptide-1- amide (GLP-1) is a member of the pro-glucagon incretin family with insulinomimetic, insulinotropic, and glucagonostatic actions whose metabolic effects favor glucose uptake. 11 Todd et al 12 and Zander et al 13 confirmed in trials of GLP-1 for type 2 diabetes that GLP-1 activity ceases at glucose levels<4 mM (72 mg/dl). This property obviates the need for concomitant glucose infusion.…”

Section: Glp-1 As a Therapeutic Alternative To Insulin-mediated Glucomentioning

confidence: 98%

Glucagon‐like Peptide‐1 and Myocardial Protection: More than Glycemic Control

Fields

Patterson

Karnik

et al. 2009

Clinical Cardiology

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Pharmacologic intervention for the failing heart has traditionally targeted neurohormonal activation and ventricular remodeling associated with cardiac dysfunction. Despite the multitude of agents available for the treatment of heart failure, it remains a highly prevalent clinical syndrome with substantial morbidity and mortality, necessitating alternative strategies of targeted management. One such area of interest is the ability to modulate myocardial glucose uptake and its impact on cardioprotection. Glucose‐insulin‐potassium (GIK) infusions have been studied for decades, with conflicting results regarding benefit in acute myocardial infarction. Based on the same concepts, glucagon‐like peptide‐1‐[7–36] amide (GLP‐1) has recently been demonstrated to be a more effective alternative in left ventricular (LV) systolic dysfunction. This paper provides a review on the current evidence supporting the use of GLP‐1 in both animal models and humans with ischemic and nonischemic cardiomyopathy. Copyright © 2009 Wiley Periodicals, Inc.

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Section: Glp-1 As a Therapeutic Alternative To Insulin-mediated Glucomentioning

confidence: 98%

Glucagon‐like Peptide‐1 and Myocardial Protection: More than Glycemic Control

Fields

Patterson

Karnik

et al. 2009

Clinical Cardiology

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“…However, in another study, bedtime injection of liraglutide modestly decreased postmeal glucagon [100]. Zander and colleagues reported the first longer-term study of GLP-1 based therapy in patients with type 2 diabetes [101]. They found that a 6-week continuous subcutaneous infusion of GLP-1 did not affect fasting or 8-h mean plasma glucagon, as compared with saline infusion, but there was a tendency for glucagon to be lower after 1 and 6 weeks of treatment, and fasting and postmeal glucose were substantially reduced.…”

Section: Acute Effects Of Exogenous and Endogenous Glp-1 On Alpha Celmentioning

confidence: 98%

Alpha cell function in health and disease: influence of glucagon-like peptide-1

Dunning¹,

2005

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Although there is abundant evidence that hyperglucagonaemia plays a key role in the development of hyperglycaemia in type 2 diabetes, efforts to understand and correct this abnormality have been overshadowed by the emphasis on insulin secretion and action. However, recognition that the incretin hormone glucagon-like peptide-1 (GLP-1) exerts opposing effects on glucagon and insulin secretion has revived interest in glucagon, the neglected partner of insulin, in the bihormonal hypothesis. In healthy subjects, glucagon secretion is regulated by a variety of nutrient, neural and hormonal factors, the most important of which is glucose. The defect in alpha cell function that occurs in type 2 diabetes reflects impaired glucose sensing. GLP-1 inhibits glucagon secretion in vitro and in vivo in experimental animals, and suppresses glucagon release in a glucose-dependent manner in healthy subjects. This effect is also evident in diabetic patients, but GLP-1 does not inhibit glucagon release in response to hypoglycaemia, and may even enhance it. Early clinical studies with agents acting through GLP-1 signalling mechanisms (e.g. exenatide, liraglutide and vildagliptin) suggest that GLP-1 can improve alpha cell glucose sensing in patients with type 2 diabetes. Therapeutic approaches based around GLP-1 have the potential to improve both alpha cell and beta cell function, and could be of benefit in patients with a broad range of metabolic disorders.

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“…It even reduced fasting and postprandial glucose levels after buccal absorption of a tablet containing 119 nmol of GLP-1 (Gutniak et al, 1997). Of particular importance were two studies of the effects of 6 weeks and 3 months continuous subcutaneous infusion of GLP-1 via MiniMed pumps in subjects with T2DM Zander et al, 2002). In the first study GLP-1 at a dose of 4.9 pmol/kg.min caused a reduction in fasting glucose (by approximately 80 mg/dl) and hemoglobin A 1c (by 1.3%) (Zander et al, 2002).…”

Section: Native Glp-1 and Treatment Of Diabetesmentioning

confidence: 99%

“…Of particular importance were two studies of the effects of 6 weeks and 3 months continuous subcutaneous infusion of GLP-1 via MiniMed pumps in subjects with T2DM Zander et al, 2002). In the first study GLP-1 at a dose of 4.9 pmol/kg.min caused a reduction in fasting glucose (by approximately 80 mg/dl) and hemoglobin A 1c (by 1.3%) (Zander et al, 2002). Body weight was slightly decreased, fasting free fatty acids were also reduced, and the treatment was well tolerated with few adverse events.…”

Section: Native Glp-1 and Treatment Of Diabetesmentioning

confidence: 99%

Mechanisms of action of glucagon-like peptide 1 in the pancreas

Doyle

Egan

2007

Pharmacology & Therapeutics

556

445

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Glucagon-like peptide-1 is a hormone that is encoded in the proglucagon gene. It is mainly produced in enteroendocrine L cells of the gut and is secreted into the blood stream when food containing fat, protein hydrolysate and/or glucose enters the duodenum. Its particular effects on insulin and glucagon secretion have generated a flurry of research activity over the past twenty years culminating in a naturally occurring GLP-1 receptor agonist, exendin-4, now being used to treat type 2 diabetes. GLP-1 engages a specific G-protein coupled receptor that is present in tissues other than the pancreas (brain, kidney, lung, heart, major blood vessels). The most widely studied cell activated by GLP-1 is the insulin-secreting beta cell where its defining action is augmentation of glucose-induced insulin secretion. Upon GLP-1 receptor activation, adenylyl cyclase is activated and cAMP generated, leading, in turn, to cAMP-dependent activation of second messenger pathways, such as the PKA and Epac pathways. As well as short-term effects of enhancing glucose-induced insulin secretion, continuous GLP-1 receptor activation also increases insulin synthesis, and beta cell proliferation and neogenesis. Although these latter effects cannot be currently monitored in humans, there are substantial improvements in glucose tolerance and increases in both first phase and plateau phase insulin secretory responses in type 2 diabetic patients treated with exendin-4. This review we will focus on the effects resulting from GLP-1 receptor activation in islets of Langerhans

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Effect of 6-week course of glucagon-like peptide 1 on glycaemic control, insulin sensitivity, and β-cell function in type 2 diabetes: a parallel-group study

Cited by 1,188 publications

References 31 publications

Glucagon‐like Peptide‐1 and Myocardial Protection: More than Glycemic Control

Glucagon‐like Peptide‐1 and Myocardial Protection: More than Glycemic Control

Alpha cell function in health and disease: influence of glucagon-like peptide-1

Mechanisms of action of glucagon-like peptide 1 in the pancreas

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