GLP-1 for type 2 diabetes

Åhrén, Bo

doi:10.1016/j.yexcr.2011.01.010

Cited by 85 publications

(65 citation statements)

References 39 publications

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“…It has been hypothesized that catecholamines, which decrease insulin levels and stimulate melatonin synthesis, control insulin-melatonin interactions. Thus, it is important to note that norepinephrine is the most decisive stimulator of melatonin synthesis, whereas epinephrine has an inhibitory effect on insulin secretion mediated through α2 receptors [176,177]. In contrast, through the activation of β2 receptors, which are Gs mediated, norepinephrine stimulates insulin secretion [176].…”

Section: Biological Relevance Of Melatonin-insulin Antagonisms In mentioning

confidence: 99%

Melatonin and Pancreatic Islets: Interrelationships between Melatonin, Insulin and Glucagon

Peschke

Bähr

Mühlbauer

2013

IJMS

135

126

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The pineal hormone melatonin exerts its influence in the periphery through activation of two specific trans-membrane receptors: MT1 and MT2. Both isoforms are expressed in the islet of Langerhans and are involved in the modulation of insulin secretion from β-cells and in glucagon secretion from α-cells. De-synchrony of receptor signaling may lead to the development of type 2 diabetes. This notion has recently been supported by genome-wide association studies identifying particularly the MT2 as a risk factor for this rapidly spreading metabolic disturbance. Since melatonin is secreted in a clearly diurnal fashion, it is safe to assume that it also has a diurnal impact on the blood-glucose-regulating function of the islet. This factor has hitherto been underestimated; the disruption of diurnal signaling within the islet may be one of the most important mechanisms leading to metabolic disturbances. The study of melatonin–insulin interactions in diabetic rat models has revealed an inverse relationship: an increase in melatonin levels leads to a down-regulation of insulin secretion and vice versa. Elucidation of the possible inverse interrelationship in man may open new avenues in the therapy of diabetes.

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Section: Biological Relevance Of Melatonin-insulin Antagonisms In mentioning

confidence: 99%

Melatonin and Pancreatic Islets: Interrelationships between Melatonin, Insulin and Glucagon

Peschke

Bähr

Mühlbauer

2013

IJMS

135

126

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“…5,6 Because there are few drugs available that can preserve or protect β-cells, any such therapy would revolutionize diabetes treatment. One of the most recent advancement in antidiabetic medication is the use of incretin-based therapies (i.e., glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors 7,8 ). Glucagon-like peptide-1 receptor agonists increase insulin secretion in a glucosedependent manner, resulting in a low risk of hypoglycemia, and more importantly, offering a weight loss benefit when compared with insulin administration.…”

Section: Introductionmentioning

confidence: 99%

Overcoming Insulin Insufficiency by Forced Follistatin Expression in β -cells of db/db Mice

et al. 2015

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Diabetes poses a substantial burden to society as it can lead to serious complications and premature death. The number of cases continues to increase worldwide. Two major causes of diabetes are insulin resistance and insulin insufficiency. Currently, there are few antidiabetic drugs available that can preserve or protect β-cell function to overcome insulin insufficiency in diabetes. We describe a therapeutic strategy to preserve β-cell function by overexpression of follistatin (FST) using an AAV vector (AAV8-Ins-FST) in diabetic mouse model. Overexpression of FST in the pancreas of db/db mouse increased β-cell islet mass, decreased fasting glucose level, alleviated diabetic symptoms, and essentially doubled lifespan of the treated mice. The observed islet enlargement was attributed to β-cell proliferation as a result of bioneutralization of myostatin and activin by FST. Overall, our study indicates overexpression of FST in the diabetic pancreas preserves β-cell function by promoting β-cell proliferation, opening up a new therapeutic avenue for the treatment of diabetes.

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“…Reducing the hyperglucagonemia is therefore an important target for the treatment of diabetes (4). Hyperglucagonemia is targeted by glucagon-like peptide 1 (GLP-1) and, consequently, by the GLP-1 receptor agonists (1,(5)(6)(7)(8). However, preserving a functional glucose counterregulation is critically important for glucose-lowering treatment to prevent hypoglycemia (9,10).…”

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confidence: 99%

Effect of the GLP-1 Receptor Agonist Lixisenatide on Counterregulatory Responses to Hypoglycemia in Subjects With Insulin-Treated Type 2 Diabetes

2015

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OBJECTIVECounterregulatory responses are critical to prevent hypoglycemia in subjects with type 2 diabetes. This is particularly important in insulin-treated patients. This study explored the effect of the glucagon-like peptide 1 receptor agonist lixisenatide on the hormonal counterregulatory responses to insulin-induced hypoglycemia when added to basal insulin therapy in subjects with type 2 diabetes. RESEARCH DESIGN AND METHODSThe study was a single-center, double-blind, randomized, placebo-controlled crossover study involving 18 subjects with type 2 diabetes (11 males) with a mean age of 55 years, diabetes duration of 12 years, HbA 1c level of 7.7%, fasting blood glucose (FBG) concentration of 9.7 mmol/L, and a BMI of 33 kg/m 2 , who were treated with basal insulin (mean duration 7 years, daily dose 39 units/day) and metformin (mean daily dose 2.1 g). Subjects received treatment with lixisenatide or placebo for 6 weeks in random order, with a 4-week washout period in between. After 6 weeks of treatment, subjects underwent a two-step hyperinsulinemic hypoglycemic clamp at 3.5 and 2.8 mmol/L. RESULTSAfter 6 weeks of treatment, HbA 1c and FBG levels were lower after lixisenatide therapy than after placebo therapy. At the hypoglycemic level of 3.5 mmol/L, glucagon and epinephrine levels were significantly lower during lixisenatide treatment than during placebo treatment, whereas at 2.8 mmol/L glucagon and epinephrine levels did not differ between the subjects. Cortisol, pancreatic polypeptide, and norepinephrine levels did not differ significantly between the treatments. CONCLUSIONSGlucagon and epinephrine levels are reduced by lixisenatide at a concentration of 3.5 mmol/L, but their counterregulatory responses to deep hypoglycemia at a concentration of 2.8 mmol/L are sustained during treatment with lixisenatide in combination with basal insulin. Clinical trial reg. nos. NCT02020629, clinicaltrials .gov, and EudraCT2012-004959-36, https:// www.clinicaltrialsregister.eu/.

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GLP-1 for type 2 diabetes

Cited by 85 publications

References 39 publications

Melatonin and Pancreatic Islets: Interrelationships between Melatonin, Insulin and Glucagon

Melatonin and Pancreatic Islets: Interrelationships between Melatonin, Insulin and Glucagon

Overcoming Insulin Insufficiency by Forced Follistatin Expression in β -cells of db/db Mice

Effect of the GLP-1 Receptor Agonist Lixisenatide on Counterregulatory Responses to Hypoglycemia in Subjects With Insulin-Treated Type 2 Diabetes

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