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Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
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The pancreatic islets comprising only 1%-2% of the volume are highly vascularized and innervated mini-organs. They contain five endocrine cell types, including β cells that secrete insulin, which is synthesized as a single polypeptide chain, preproinsulin, processed to proinsulin, and finally to insulin and C-peptide. This process is complex and regulated, involving the Golgi complex, the endoplasmic reticulum, and the secretory granules of the β cell.
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Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
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Insulin is released by beta cells of the pancreas when blood glucose levels are high. It facilitates glucose absorption and utilization in insulin-dependent cells with insulin receptors on their plasma membranes. Insulin promotes glucose uptake by increasing the number of glucose transport proteins in the cell membrane, allowing glucose to enter the cell. As a result, glucose utilization and ATP production are enhanced.
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Repaglinide (Prandin) and Nateglinide (Starlix), known as glinides, are oral insulin secretagogues that stimulate insulin release from pancreatic β cells by closing the ATP-sensitive potassium channels (KATP channel). Repaglinide controls insulin release from pancreatic β cells by managing potassium efflux. It shares two binding sites with sulfonylureas and also has a unique site, indicating overlapping mechanisms of action. With a rapid onset and a 4-7 hour duration, it effectively...
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Without prolonged fasting, healthy individuals maintain blood glucose levels above 3.5 mM due to a well-adapted neuroendocrine counterregulatory system that effectively prevents acute hypoglycemia, a potentially life-threatening condition. The primary clinical scenarios for hypoglycemia encompass diabetes treatment, inappropriate production of endogenous insulin or insulin-like substances by tumors, and the use of glucose-lowering agents in non-diabetic individuals. Notably, hypoglycemia in the...
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Glucagon-like peptide 1 (GLP-1).

T D Müller1, B Finan2, S R Bloom3

  • 1Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany; Department of Pharmacology and Experimental Therapy, Institute of Experimental and Clinical Pharmacology and Toxicology, Eberhard Karls University Hospitals and Clinics, Tübingen, Germany.

Molecular Metabolism
|November 27, 2019
PubMed
Summary
This summary is machine-generated.

Glucagon-like peptide-1 (GLP-1) is a versatile hormone with significant metabolic and therapeutic potential. Its diverse functions are being harnessed for treating type-2 diabetes, obesity, and neurodegenerative disorders.

Keywords:
DiabetesGLP-1GlucagonIncretinInsulinObesity

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Area of Science:

  • Endocrinology and Pharmacology

Background:

  • Glucagon-like peptide-1 (GLP-1) is a pleiotropic hormone with extensive metabolic functions beyond its incretin role.
  • GLP-1 influences insulin secretion, gastric emptying, appetite, natriuresis, and beta-cell proliferation.
  • It also exhibits cardio- and neuroprotective effects, anti-inflammatory properties, and impacts learning and memory.

Purpose of the Study:

  • To provide a comprehensive review of the multifaceted nature of GLP-1.
  • To discuss the pharmacology of GLP-1 and its receptor agonists.
  • To explore the therapeutic implications of GLP-1 in various diseases.

Main Methods:

  • Literature review of GLP-1's biological functions.
  • Analysis of GLP-1 receptor agonist clinical applications.
  • Discussion of ongoing and potential therapeutic uses.

Main Results:

  • GLP-1 receptor agonists are clinically established for type-2 diabetes treatment.
  • Pharmacotherapies based on GLP-1 are under evaluation for obesity.
  • GLP-1's broad effects suggest potential in neurodegenerative disorders.

Conclusions:

  • GLP-1 is a key hormone with diverse therapeutic applications.
  • Modified GLP-1 analogs demonstrate significant clinical utility.
  • Further research into GLP-1-based treatments holds promise for multiple diseases.