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Related Concept Videos

Hormones Regulating Blood Glucose01:16

Hormones Regulating Blood Glucose

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.
In addition to accelerating glucose uptake and utilization, insulin has...
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion01:27

Glucose Homeostasis: Pancreatic Islets and Insulin Secretion

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.
Insulin and C-peptide are co-secreted in...
Oral Hypoglycemic Agents: Glinides01:06

Oral Hypoglycemic Agents: Glinides

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 manages...
Oral Hypoglycemic Agents: α-Glucosidase Inhibitors01:19

Oral Hypoglycemic Agents: α-Glucosidase Inhibitors

α-glucosidase inhibitors, including acarbose (Precose), miglitol (Glyset), and voglibose (Voglib) (primarily available in Asia), are drugs that control blood sugar levels by delaying the digestion of starch and disaccharides. They achieve this by inhibiting α-glucosidase enzymes in the intestine, which slow the absorption of carbohydrates in the intestine, which in turn leads to a prolonged release of the glucoregulatory hormone GLP-1 from intestinal L-cells.
Acarbose and miglitol are typically...
Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

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.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by the...
Dipeptidyl Peptidase 4 Inhibitors01:23

Dipeptidyl Peptidase 4 Inhibitors

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 significant...

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Related Experiment Video

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Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice
11:10

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Dipeptidyl peptidase IV inhibition enhances the intestinotrophic effect of glucagon-like peptide-2 in rats and mice.

B Hartmann1, J Thulesen, H Kissow

  • 1Department of Medical Physiology, The Panum Institute, University of Copenhagen, Denmark.

Endocrinology
|November 23, 2000
PubMed
Summary
This summary is machine-generated.

Glucagon-like peptide-2 (GLP-2) is less potent in rats due to enzyme degradation. Inhibiting dipeptidyl peptidase IV (DPP-IV) with valine-pyrrolidide (VP) significantly enhances GLP-2's intestinal growth effects in both rats and mice.

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Mixed Primary Cultures of Murine Small Intestine Intended for the Study of Gut Hormone Secretion and Live Cell Imaging of Enteroendocrine Cells
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Important Endpoints and Proliferative Markers to Assess Small Intestinal Injury and Adaptation using a Mouse Model of Chemotherapy-Induced Mucositis
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Mixed Primary Cultures of Murine Small Intestine Intended for the Study of Gut Hormone Secretion and Live Cell Imaging of Enteroendocrine Cells
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Important Endpoints and Proliferative Markers to Assess Small Intestinal Injury and Adaptation using a Mouse Model of Chemotherapy-Induced Mucositis
07:05

Important Endpoints and Proliferative Markers to Assess Small Intestinal Injury and Adaptation using a Mouse Model of Chemotherapy-Induced Mucositis

Published on: May 12, 2019

Area of Science:

  • Gastroenterology
  • Pharmacology
  • Endocrinology

Background:

  • Glucagon-like peptide-2 (GLP-2) promotes intestinal growth.
  • GLP-2's efficacy is limited in rats due to rapid degradation by dipeptidyl peptidase IV (DPP-IV).

Purpose of the Study:

  • To investigate the pharmacokinetics and intestinotrophic effects of GLP-2 in rats and mice.
  • To evaluate the impact of DPP-IV inhibition on GLP-2's survival and efficacy.

Main Methods:

  • Subcutaneous injection of GLP-2 with or without the DPP-IV inhibitor valine-pyrrolidide (VP) in rats and mice.
  • Measurement of plasma intact GLP-2 concentrations via RIA.
  • Assessment of body weight, intestinal weight, length, and morphometric parameters after treatment.

Main Results:

  • DPP-IV inhibition with VP increased plasma concentrations of intact GLP-2 in rats.
  • GLP-2 plus VP significantly enhanced small-bowel weight in rats compared to GLP-2 alone or controls.
  • In mice, co-administration of GLP-2 with VP yielded a comparable growth effect to a higher dose of GLP-2 alone.

Conclusions:

  • DPP-IV inhibition effectively reduces GLP-2 degradation in rats.
  • DPP-IV inhibition markedly potentiates the intestinotrophic effects of GLP-2 in both rats and mice.
  • DPP-IV inhibition represents a promising strategy to enhance the therapeutic efficacy of GLP-2.