Related Experiment Video

Updated: Jun 21, 2025

Measuring Relative Insulin Secretion using a Co-Secreted Luciferase Surrogate
05:58

Measuring Relative Insulin Secretion using a Co-Secreted Luciferase Surrogate

Published on: June 25, 2019

7.4K

Hypertonicity during a rapid rise in D-glucose mediates first-phase insulin secretion

Varun Kamat1, Ian R Sweet1

  • 1University of Washington Medicine Diabetes Institute, University of Washington, Seattle, WA, United States.

Frontiers in Endocrinology
|July 11, 2024
PubMed

Insights

Biphasic insulin secretion, crucial for glucose regulation, is driven by osmotic changes, not just metabolism. This finding redefines our understanding of first-phase insulin release in pancreatic islets.

Area of Science:

  • Endocrinology
  • Metabolic Research
  • Cell Biology

Background:

  • Biphasic insulin secretion is a key pancreatic islet function.
  • Loss of first-phase insulin secretion is linked to Type 2 diabetes.
  • First-phase insulin secretion is known to be triggered by rapid glucose changes.

Purpose of the Study:

  • To test the hypothesis that islet response to glucose involves both metabolic and osmotic effects.
  • To investigate the role of hypertonicity in driving first-phase insulin secretion.

Main Methods:

  • Perifusion analysis of rat, mouse, and human islets.
  • Measured insulin secretion rate (ISR) and regulatory parameters.
  • Used D-glucose combined with membrane-impermeable carbohydrates (L-glucose or mannitol) to isolate osmotic effects.

Main Results:

  • First-phase responses were dependent on tonicity changes, not solely glucose metabolism.
  • Rapid increases in L-glucose (without D-glucose change) mimicked D-glucose-induced first-phase responses.
  • H89 abolished first-phase insulin secretion but not the first-phase calcium response.

Conclusions:

  • A new model suggests first-phase insulin secretion is driven by hypertonicity-induced kinase activation.
  • This osmotic effect amplifies second-phase insulin secretion.
  • The findings offer novel insights into glucose-stimulated insulin secretion mechanisms.
Abstract

Keywords:
L-type calcium channelbiphasic insulin secretioncAMPfirst phasehypertonicityinsulin secretionisletosmotic pressure

More Related Videos

Homogeneous Time-resolved Förster Resonance Energy Transfer-based Assay for Detection of Insulin Secretion07:30

Homogeneous Time-resolved Förster Resonance Energy Transfer-based Assay for Detection of Insulin Secretion

Published on: May 10, 2018

9.2K
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

20.0K

Related Concept Videos

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...
1.2K
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...
4.9K
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...
3.2K
Glucose Absorption Into the Small Intestine01:26

Glucose Absorption Into the Small Intestine

Complex carbohydrates consumed cannot be absorbed into the small intestine in their original form. First, they must be hydrolyzed to a monosaccharide form such as glucose or galactose. These monosaccharides are then transported across the intestinal membrane and into the blood via transcellular transport. The intestinal epithelial cells allow the movement of these monosaccharides with a defined 'entry' through membrane transporter proteins present on their apical membrane and...
31.6K
Insulin: The Receptor and Signaling Pathways01:28

Insulin: 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...
1.2K
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...
313