Related Experiment Video

Updated: Jul 18, 2026

Live Images of GLUT4 Protein Trafficking in Mouse Primary Hypothalamic Neurons Using Deconvolution Microscopy
08:47

Live Images of GLUT4 Protein Trafficking in Mouse Primary Hypothalamic Neurons Using Deconvolution Microscopy

Published on: December 7, 2017

Cdk5-dependent regulation of glucose-stimulated insulin secretion

Fan-Yan Wei1, Kazuaki Nagashima, Toshio Ohshima

  • 1Department of Physiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, Japan.

Nature Medicine
|September 13, 2005
PubMed

Insights

Inhibiting cyclin-dependent kinase 5 (Cdk5) boosts glucose-stimulated insulin secretion without causing hypoglycemia. This discovery offers a new therapeutic target for managing diabetes by improving pancreatic beta cell function.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Pharmacology

Background:

  • Diabetes mellitus requires tight glycemic control to prevent complications.
  • Current hyperglycemia treatments targeting K(ATP) channels risk hypoglycemia.
  • Novel therapeutic targets for glucose-stimulated insulin secretion are needed.

Purpose of the Study:

  • To investigate the role of cyclin-dependent kinase 5 (Cdk5) in regulating insulin secretion.
  • To explore Cdk5 as a potential drug target for diabetes treatment.

Main Methods:

  • Utilized MIN6 cells and pancreatic islets to study Cdk5 activity.
  • Employed p35-knockout mice to assess Cdk5's in vivo role.
  • Measured Ca(2+) influx and L-type voltage-dependent Ca(2+) channel (L-VDCC) activity.

Main Results:

  • Cdk5 inhibition enhanced glucose-stimulated insulin secretion in beta cells.
  • Cdk5 inhibition increased Ca(2+) influx via L-VDCC in response to high glucose.
  • Cdk5 phosphorylates L-VDCC at Ser783, inhibiting its activity.

Conclusions:

  • Cdk5/p35 signaling pathway regulates glucose-stimulated insulin secretion.
  • Inhibiting Cdk5 activity presents a promising therapeutic strategy for diabetes.
  • Targeting Cdk5 may offer improved glycemic control with reduced hypoglycemia risk.

More Related Videos

Studying the Hypothalamic Insulin Signal to Peripheral Glucose Intolerance with a Continuous Drug Infusion System into the Mouse Brain08:32

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

Published on: January 4, 2018

Measuring Relative Insulin Secretion using a Co-Secreted Luciferase Surrogate05:58

Measuring Relative Insulin Secretion using a Co-Secreted Luciferase Surrogate

Published on: June 25, 2019

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-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,...
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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...
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: 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 this inhibition is released...