Related Experiment Video

Updated: Jul 16, 2026

Isolated Pancreatic Islet Treatment and Apoptosis Measurement
09:36

Isolated Pancreatic Islet Treatment and Apoptosis Measurement

Published on: May 2, 2025

Sulfonylurea and glinide reduce insulin content, functional expression of K(ATP) channels, and accelerate apoptotic

Akira Takahashi1, Kazuaki Nagashima, Akihiro Hamasaki

  • 1Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.

Diabetes Research and Clinical Practice
|February 24, 2007
PubMed

Insights

Chronic use of oral hypoglycemic agents like sulfonylureas and glinides impairs insulin secretion by reducing ATP-sensitive K(+) (K(ATP)) channels and accelerating beta-cell death, leading to secondary treatment failure in type 2 diabetes.

Area of Science:

  • Endocrinology
  • Pharmacology
  • Cell Biology

Background:

  • Oral hypoglycemic agents, including sulfonylureas and glinides, are widely used for type 2 diabetes management.
  • Chronic exposure to these agents can lead to secondary treatment failure, but the underlying mechanisms are not fully understood.

Purpose of the Study:

  • To investigate the effects of chronic exposure to sulfonylureas and glinides on insulin secretion in pancreatic beta-cells.
  • To compare the impact of different oral hypoglycemic agents on K(ATP) channels, insulin content, and beta-cell apoptosis.

Main Methods:

  • Pancreatic beta-cells were chronically exposed to sulfonylureas (glibenclamide, tolbutamide) and a glinide (nateglinide).
  • Insulin secretion, insulin content, functional ATP-sensitive K(+) (K(ATP)) channels, and voltage-dependent Ca(2+) channels (VDCCs) were assessed.
  • Apoptotic beta-cell death was measured.

Main Results:

  • Chronic exposure to sulfonylureas and glinides similarly reduced insulin content and the number of functional K(ATP) channels.
  • Functional expression of VDCCs remained unchanged compared to untreated cells.
  • All three agents accelerated apoptotic beta-cell death.

Conclusions:

  • Impaired insulin secretion after chronic sulfonylurea and glinide treatment is linked to reduced insulin content, fewer functional K(ATP) channels, and increased beta-cell apoptosis.
  • These mechanisms contribute to secondary treatment failure in type 2 diabetes pharmacotherapy.
  • Findings offer insights into long-term therapeutic strategies for type 2 diabetes.

More Related Videos

Glucose Uptake Measurement and Response to Insulin Stimulation in In Vitro Cultured Human Primary Myotubes08:03

Glucose Uptake Measurement and Response to Insulin Stimulation in In Vitro Cultured Human Primary Myotubes

Published on: June 25, 2017

Related Concept Videos

Oral Hypoglycemic Agents: Sulfonylureas01:17

Oral Hypoglycemic Agents: Sulfonylureas

Sulfonylureas are oral hypoglycemic agents utilized in treating type 2 diabetes. They are characterized by their unique sulfonylurea chemical structure. The family of sulfonylureas is divided into generations. First-generation sulfonylureas, including tolbutamide (Orinase), chlorpropamide (Diabinese), and tolazamide (Tolinase), trigger insulin release from pancreatic β cells and enhance peripheral tissues' insulin sensitivity. The second-generation members, such as glipizide (Glucotrol),...
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...
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...
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 glucose levels...
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...
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...