Related Experiment Video

Updated: Jun 23, 2026

Studying the Hypothalamic Insulin Signal to Peripheral Glucose Intolerance with a Continuous Drug Infusion System into the Mouse Brain
08:32

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

Published on: January 4, 2018

Regulation of PKD by the MAPK p38delta in insulin secretion and glucose homeostasis

Grzegorz Sumara1, Ivan Formentini, Stephan Collins

  • 1Institute of Cell Biology, ETH Zurich, CH-8093 Zurich, Switzerland.

Cell
|January 13, 2009
PubMed

Insights

Mice lacking the p38delta protein kinase showed improved glucose tolerance and insulin secretion. This pathway regulates pancreatic beta cell function and survival, offering potential diabetes mellitus targets.

Area of Science:

  • Molecular biology
  • Endocrinology
  • Diabetes research

Background:

  • Pancreatic beta cell dysfunction is central to diabetes mellitus.
  • Mitogen-activated protein kinase (MAPK) p38delta's role in beta cell function is not fully understood.

Purpose of the Study:

  • To investigate the role of p38delta in regulating pancreatic beta cell function and glucose homeostasis.
  • To identify novel regulators of insulin secretion and beta cell survival.

Main Methods:

  • Utilized knockout mouse models lacking p38delta.
  • Assessed glucose tolerance and insulin secretion.
  • Investigated protein kinase D (PKD) activation and phosphorylation status.
  • Examined beta cell response to oxidative stress and high-fat diet.

Main Results:

  • Mice lacking p38delta exhibited enhanced glucose tolerance and insulin secretion.
  • p38delta deletion led to increased protein kinase D (PKD) activation.
  • p38delta negatively regulates PKD1, a key mediator of insulin exocytosis.
  • p38delta null mice were protected against diet-induced insulin resistance and oxidative stress.

Conclusions:

  • The p38delta-PKD signaling pathway is a critical regulator of pancreatic beta cell insulin secretion and survival.
  • Targeting this pathway may offer therapeutic strategies for diabetes mellitus.

More Related Videos

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway07:15

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

Published on: August 23, 2024

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice10:31

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice

Published on: May 2, 2025

Related Concept Videos

Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
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,...
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...