Related Experiment Video
Updated: Jul 22, 2026
10:39
Preparation of Pancreatic Acinar Cells for the Purpose of Calcium Imaging, Cell Injury Measurements, and Adenoviral Infection
Published on: July 5, 2013
Calpains play a role in insulin secretion and action
S K Sreenan1, Y P Zhou, K Otani
1Deppartment of Medicine, the University of Chicago, Chicago, Illinois, USA.
Diabetes
|August 28, 2001
Summary
Calpain inhibitors enhance glucose-stimulated insulin secretion in mouse islets by accelerating insulin granule release. However, they reduce insulin
Area of Science:
- Biochemistry
- Cell Biology
- Endocrinology
Background:
- Calpain-10 gene variations are linked to type 2 diabetes susceptibility.
- Calpains are cysteine proteases involved in cellular functions.
- Calpain-sensitive pathways may regulate insulin secretion and action.
Purpose of the Study:
- To investigate the role of calpains in insulin secretion and action.
- To determine the effect of calpain inhibitors on pancreatic islet function.
- To examine calpain's influence on glucose transport in muscle and adipocytes.
Main Methods:
- Short-term exposure (4-h) of mouse pancreatic islets to calpain inhibitors (calpain inhibitor II, E-64-d).
- Measurement of insulin secretory response to glucose.
- Assessment of intracellular Ca2+ levels and glucose metabolism.
- Evaluation of insulin-mediated glucose transport in muscle strips and adipocytes.
Main Results:
- Calpain inhibitors dose-dependently increased glucose-stimulated insulin secretion in mouse islets (above 8 mmol/l glucose).
- Inhibition of calpains accelerated insulin granule exocytosis without altering Ca2+ or glucose metabolism.
- Calpain inhibitors reduced insulin-mediated glucose transport and glycogen incorporation in muscle and adipocytes.
Conclusions:
- Calpains play a role in regulating both insulin secretion and insulin action.
- Targeting calpain pathways may offer therapeutic strategies for type 2 diabetes.
- Calpain inhibition affects insulin secretion via exocytosis and insulin action via glucose transport.
Related Concept Videos
01:05Insulin 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...
01:25cAMP-dependent Protein Kinase Pathways
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
01:16Cells and Secretions of the Pancreas
The pancreas, a vital organ within the abdominal cavity, plays dual roles in the digestive and endocrine systems, collaborating with exocrine and endocrine cells to maintain optimal digestion and blood sugar levels.
Exocrine function is carried out by acinar cells, organized into clusters known as acini. These cells contribute to digestion by releasing substantial quantities of enzyme-rich, alkaline digestive juices.
Concurrently, the dispersed clusters of endocrine cells throughout the...
Exocrine function is carried out by acinar cells, organized into clusters known as acini. These cells contribute to digestion by releasing substantial quantities of enzyme-rich, alkaline digestive juices.
Concurrently, the dispersed clusters of endocrine cells throughout the...
01:16Hormones 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...
In addition to accelerating glucose uptake and utilization, insulin has...
01:27Glucose 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 and C-peptide are co-secreted in...
01:28Insulin: The Receptor and Signaling Pathways
Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but this inhibition is released...