Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING LLC
GLOBETECH PUBLISHING LLC
PURITAN MEDICAL

Loss of Beta-Cell EPAC2A Activity Linked to Development of Type II Diabetes

By BiotechDaily International staff writers
Posted on 25 Apr 2013
Diabetes researchers have discovered how the protein EPAC2A (guanine nucleotide exchange factors for Ras-like small GTPases) affects glucose metabolism and how loss of this protein activity may contribute to the development of type II diabetes.

Incretin hormone action on beta cells stimulates in parallel two different intracellular cyclic AMP-dependent signaling branches mediated by PKA (protein kinase A) and EPAC2A. Both pathways contribute towards potentiation of glucose-stimulated insulin secretion. However, the overall functional role of EPAC2A in beta cells as it relates to in vivo glucose homeostasis has not been well understood.

Incretins are a group of gastrointestinal hormones that cause an increase in the amount of insulin released from the beta-cells of the islets of Langerhans after eating, even before blood glucose levels become elevated. They also slow the rate of absorption of nutrients into the blood stream by reducing gastric emptying and may directly reduce food intake. Furthermore, they also inhibit glucagon release from the alpha cells of the islets of Langerhans. The two main candidate molecules that fulfill criteria for an incretin are glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP).

In the current study, investigators at Johns Hopkins University (Baltimore, MD, USA) examined the interaction between incretins and EPAC2A. To do this they genetically engineered a line of mice lacking the gene for EPAC2A production.

Results published in the April 11, 2013, online edition of the journal Diabetes revealed that EPAC2A deficiency did not impact glucose-stimulated insulin secretion in the knockout mice under normal conditions. However, when the mice were exposed to diet-induced insulin resistance or incretin hormone stimulation of beta cells, EPAC2A was required for the increased beta-cell response to secretory demand. Under these circumstances, EPAC2A was required for potentiating the early dynamic increase in islet calcium levels after glucose stimulation, which is reflected in potentiated first phase insulin secretion.

“It is as if during these extreme conditions, the body calls upon EPAC2 as backup to help it balance insulin supply and demand,” said senior author Dr. Mehboob Hussain, associate professor of pediatrics, medicine, and biological chemistry at Johns Hopkins University. “Drugs that precision-target failing pancreatic cells and restore or boost their function have become the holy grail of diabetes research. We believe that our finding establishes a pathway to do just that.”

Related Links:
Johns Hopkins University


Channels

Drug Discovery

view channel
Image: A new micelle delivery system for the protective polyphenols resveratrol and quercetin (mRQ) may have value in cancer chemotherapy (Photo courtesy of Oregon State University).

Micelles Containing Resveratrol and Quercetin Reverse Doxorubicin Cardiotoxicity

Cancer researchers blocked the toxic effects of the cancer drug doxorubicin (DOX) by administering it together with the plant antioxidants resveratrol and quercetin. Although in use for more than 40... Read more

Lab Technologies

view channel
Image: The Leica DM2500 LED Microscope for clinical laboratories and research applications (Photo courtesy of Leica Microsystems).

New LED Microscope Completes Line of Clinical and Research Tools

A popular microscope used for both clinical and research applications is now available with LED illumination. The Leica (Wetzlar, Germany) DM2500 and DM2500 LED microscopes represent a class of tools... Read more

Business

view channel

Teva Buys Allergan Generic Business Unit

Teva Pharmaceutical Industries (Petah Tikva, Israel) has bought the Allergan (Irvine, CA, USA) generic drugs business for USD 40.5 billion in cash and stock, solidifying its position as the world's largest generic drug maker. Under the terms of the agreement, Teva will pay USD 33.75 billion in cash and USD 6.... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.