Related Experiment Video

Updated: Aug 10, 2026

A Method for Mouse Pancreatic Islet Isolation and Intracellular cAMP Determination
12:33

A Method for Mouse Pancreatic Islet Isolation and Intracellular cAMP Determination

Published on: June 25, 2014

Imidazole antimycotics affect the activity of various ion channels and insulin secretion in mouse pancreatic B-cells

S Welker1, G Drews

  • 1Universität Tübingen, Abteilung Pharmakologie, Germany.

Naunyn-Schmiedeberg'S Archives of Pharmacology
|December 24, 1997
PubMed

Insights

Imidazole antimycotics like clotrimazole inhibit key ion currents in pancreatic B-cells, affecting insulin secretion. These drugs disrupt both ATP-sensitive potassium channels and voltage-dependent calcium and potassium channels, impacting hormone release.

Area of Science:

  • Endocrinology
  • Pharmacology
  • Cell Physiology

Background:

  • Pancreatic B-cells regulate insulin secretion through ion channel activity.
  • Antimycotic drugs, particularly those with imidazole structures, can have off-target effects on cellular functions.
  • Understanding the impact of these drugs on B-cell function is crucial for patient safety and therapeutic development.

Purpose of the Study:

  • To investigate the effects of imidazole antimycotics on ion currents in mouse pancreatic B-cells.
  • To determine the impact of these drugs on insulin secretion from isolated islets.
  • To elucidate the mechanisms by which clotrimazole affects B-cell electrophysiology and hormone release.

Main Methods:

  • Patch-clamp technique (whole-cell and inside-out configurations) to study ion currents.
  • Measurement of membrane potential in pancreatic B-cells.
  • Assessment of insulin secretion from isolated pancreatic islets.
  • Electrophysiological recordings of ATP-sensitive potassium (K+ ATP) channels, voltage-dependent Ca2+ and K+ channels, and hypotonicity-induced inward currents.

Main Results:

  • Clotrimazole, econazole, and ketoconazole reversibly inhibited whole-cell K+ ATP currents and depolarized B-cell membrane potential.
  • Clotrimazole inhibited single K+ ATP channel currents, suggesting a direct action.
  • Clotrimazole altered voltage-dependent Ca2+ and K+ channel activity and abolished a hypotonicity-induced inward current.
  • Clotrimazole, econazole, and ketoconazole irreversibly inhibited insulin secretion, with effects likely related to altered ion channel activity.

Conclusions:

  • Imidazole antimycotics, including clotrimazole, significantly alter the activity of multiple ion currents in pancreatic B-cells.
  • These drug-induced changes in ion channel function likely contribute to the observed inhibition of insulin secretion.
  • While effects on ion channels are evident, interference with stimulus-secretion coupling distal to membrane potential changes cannot be entirely excluded.

More Related Videos

A Murine Pancreatic Islet Cell-based Screening for Diabetogenic Environmental Chemicals07:39

A Murine Pancreatic Islet Cell-based Screening for Diabetogenic Environmental Chemicals

Published on: June 25, 2018

Glucose-Stimulated Insulin Secretion via Perfusion through the Mice Vasculature with an Intact Pancreas04:41

Glucose-Stimulated Insulin Secretion via Perfusion through the Mice Vasculature with an Intact Pancreas

Published on: July 25, 2025

Related Concept Videos

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...
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...
Insulin: Biosynthesis, Chemistry, and Preparation01:25

Insulin: Biosynthesis, Chemistry, and Preparation

The endoplasmic reticulum (ER) of pancreatic β-cells synthesizes preproinsulin, which consists of a signal peptide, A and B chains, and a C-peptide. Preproinsulin is then cleaved and folded into proinsulin, which translocates to the Golgi apparatus for sorting and packaging into secretory granules. In these granules, enzymatic clipping generates insulin and C-peptide.
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment primarily uses...
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...
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...
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...