Related Experiment Video

Updated: Jan 13, 2026

Studying the Hypothalamic Insulin Signal to Peripheral Glucose Intolerance with a Continuous Drug Infusion System into the Mouse Brain
08:32

Studying the Hypothalamic Insulin Signal to Peripheral Glucose Intolerance with a Continuous Drug Infusion System into the Mouse Brain

Published on: January 4, 2018

10.8K

Enhanced insulin secretion and sensitization in diabetic mice on chronic treatment with a transient receptor

Hirotsugu Tanaka1, Akiyoshi Shimaya, Tetsuo Kiso

  • 1Pharmacology Research Labs, Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. hirotsugu.tanaka@jp.astellas.com

Life Sciences
|February 1, 2011
PubMed
Abstract

Insights

The TRPV1 antagonist BCTC improved glucose and lipid metabolism in type 2 diabetic mice, acting as both an insulin sensitizer and secretagogue. This suggests potential for TRPV1 inhibitors in diabetes treatment.

Area of Science:

  • Pharmacology
  • Endocrinology
  • Metabolic Diseases

Background:

  • Transient Receptor Potential Vanilloid 1 (TRPV1) signaling influences insulin secretion.
  • TRPV1 antagonists may modulate glucose and lipid metabolism.
  • Ob/ob mice serve as a model for type 2 diabetes and insulin resistance.

Purpose of the Study:

  • To investigate the anti-diabetic effects of repeat BCTC administration in ob/ob mice.
  • To assess the impact of BCTC on whole-body glucose and lipid metabolism.
  • To compare BCTC's effects with a known insulin-sensitizing agent, pioglitazone.

Main Methods:

  • Repeat administration of BCTC (N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2H)-carboxamidte monohydrochloride) to ob/ob mice twice daily for four weeks.
  • Measurement of blood parameters including glucose, insulin, and triglycerides.
  • Oral glucose tolerance tests (OGTT) to evaluate glucose metabolism and insulin secretion.

Main Results:

  • BCTC treatment significantly reduced fasting glucose, triglyceride, and insulin levels.
  • The metabolic improvements induced by BCTC were comparable to those of pioglitazone.
  • BCTC administration enhanced plasma insulin secretion during OGTT, unlike pioglitazone.

Conclusions:

  • This study demonstrates the anti-diabetic pharmacological effects of the TRPV1 inhibitor BCTC.
  • TRPV1 antagonists exhibit dual actions: insulin sensitization and insulin secretion stimulation.
  • TRPV1 antagonists represent a promising new therapeutic class for type 2 diabetes mellitus.

More Related Videos

Combined Intravital Microscopy and Contrast-enhanced Ultrasonography of the Mouse Hindlimb to Study Insulin-induced Vasodilation and Muscle Perfusion08:22

Combined Intravital Microscopy and Contrast-enhanced Ultrasonography of the Mouse Hindlimb to Study Insulin-induced Vasodilation and Muscle Perfusion

Published on: March 20, 2017

9.1K
Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice11:10

Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice

Published on: November 16, 2011

95.6K

Related Concept Videos

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...
832
Oral Hypoglycemic Agents: Biguanides and Glitazones01:26

Oral Hypoglycemic Agents: Biguanides and Glitazones

Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood...
571
Insulin Secretory Vesicles01:05

Insulin Secretory Vesicles

Insulin secretory vesicles release insulin to stimulate blood glucose uptake and regulate carbohydrate metabolism. When the blood glucose levels increase, glucose enters the pancreatic β-islet cells through glucose transporters. Once inside, glucose is metabolized through glycolysis, the citric acid cycle, and the electron transport chain, producing ATP. This increase in ATP concentration closes ATP-sensitive potassium channels, leading to depolarization of the membrane and the opening of...
6.4K
Diabetes Mellitus: Overview and Type I Subtype01:22

Diabetes Mellitus: Overview and Type I Subtype

Diabetes mellitus is a chronic metabolic disorder characterized by high blood glucose levels due to inadequate insulin production, insulin resistance, or both. The condition affects millions worldwide and can significantly impact their health and quality of life.
Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks and destroys the insulin-producing beta cells in the pancreas. As a result, the body is unable to produce sufficient insulin, and individuals with...
4.8K
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...
574
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...
2.1K