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Breaking news about genomic engineering, T2DM and cancer treatments – 9/28/2015

Larry H Bernstein, MD, FCAP, Curator

LPBI

Newly Identified Biochemical Pathway Could Be Target For Insulin Control

Mon, 09/28/2015  Duke University

2.1.3.12   Breaking News about Genomic Engineering, T2DM and Cancer Treatments – 9/28/2015, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 2: CRISPR for Gene Editing and DNA Repair

In the final event leading to the development of Typ 2 diabetes, the pancreas loses its ability to secrete insulin and clear glucose from the blood. Preventing this breakdown in insulin secretion is a key goal in the fight to reduce the burden of a disease that afflicts an estimated 29 million people in the United States.

Now researchers at Duke Medicine and the University of Alberta are reporting the identification of a new biochemical pathway to control insulin secretion from islet beta cells in the pancreas, establishing a potential target for insulin control.

The study, published online Sept. 24 in the journal Cell Reports, results from a field of work called metabolomics, which uses mass spectrometry instruments to measure and trace intermediate molecules in key metabolic pathways of cells and tissues.

“The Duke group focused on metabolites in islet cells that changed in response to elevated external glucose concentrations,” said co-senior author Christopher B. Newgard, Ph.D., director of the Sarah W. Stedman Nutrition and Metabolism Center and the Duke Molecular Physiology Institute. “We found a strong increase in an intermediate in the purine/nucleotide metabolic pathway — known as adenylosuccinate, or S-AMP — in islets stimulated with glucose.”

Impairment of S-AMP production was shown to interfere with normal glucose-stimulated insulin secretion. The Duke and University of Alberta Diabetes Institute teams were also able to demonstrate that S-AMP is capable of rescuing impaired insulin secretion in islets from people with Type 2 diabetes.

Newgard said the collaborative effort between the Duke and Alberta teams also yielded a separate finding, reported online Sept. 21 in the Journal of Clinical Investigation, which describes another molecular pathway that could be a potential metabolic target for insulin control.

In that study, the research teams identified a process that works essentially like a dimmer switch to adjust how much or how little insulin is secreted when blood sugar increases. This dimmer switch appears to be broken in Type 2 diabetes, but the researchers found that its function can be restored.

“For the moment, we have two separate mechanisms, but with further study we may find that they are more connected,” Newgard said. “Whether they are independent, additive or synergistic is unknown, so we are eager to bring the two projects together to see where that may lead.”

The National Institutes of Health and the Canadian Institutes of Health Research  funded the research.

Source: Duke University

http://www.biosciencetechnology.com/news/2015/09/newly-identified-biochemical-pathway-could-be-target-insulin-control?

Tissue-Specific Molecular Biomarker Signatures of Type 2 Diabetes

An Integrative Analysis of Transcriptomics and Protein–Protein Interaction Data

Beste Calimlioglu, Kubra Karagoz, Tuba Sevimoglu, Elif Kilic, Esra Gov, Kazim Yalcin Arga

http://www.genengnews.com/media/images/AnalysisAndInsight/Sep23_2015_YOmerAkyol_Type2Diabetes1291421046.jpg

Mutual DEGs between only two different tissues/cells. [Y. Omer Akyol]

• Type 2 diabetes mellitus (T2D) is a major global health burden. A complex metabolic disease, type 2 diabetes affects multiple different tissues, demanding a ‘‘systems medicine’’ approach to biomarker and novel diagnostic discovery, not to mention data integration across omics-es (Günther et al. 2014; Montague et al. 2014; Sahu et al. 2014). The two important key determinants of T2D are the failure of peripheral tissues (such as liver, muscle, and adipose tissue) to respond to insulin doses (so-called insulin resistance), and the failure of suitable insulin secretion by pancreatic beta cells in response to increased blood glucose levels (Kaiser and Oetjen, 2014).

The duration of hyperglycemia caused by failure of betacells also affects insulin secretory capacity, mass, and apoptosis rate of beta-cells, resulting in additional alterations in several processes such as islet inflammation, amyloid deposition, critical B-cell alterations (Prentki and Nolan, 2006). On the other hand, the state of hyperglycemia dama
ges nerves and blood vessels, leading to major healthrelated issues such as cardiovascular diseases, stroke, blindness, dental problems, and diabetes-related amputations. Other complications of T2D include enhanced vulnerability to neurodegenerative diseases, presence of various cancer types, pregnancy problems, loss of mobility with aging, and depression (Musselman et al., 2003; Retnakaran et al., 2006).

Due to the high prevalence of T2D and its fateful complications, identifying the genes or genetic factors associated with the development of T2D and elucidating the mechanisms underlying the disease are crucial in prognosis, and development of personalized medicine and therapeutic strategies.

Since it is a polygenic disorder (i.e., multiple genes located on different chromosomes take active roles in the development of the disease), it is better to reveal that gene expression varies more across tissues than across individuals. Several studies reported findings on T2D gene expression profiles of
different tissues individually (Kazier et al., 2007; Cangemi et al., 2011; Misu et al., 2010; van Tienen et al., 2012; Dominguez et al., 2011). Despite individual studies exploring T2D specific genes in various tissues, studies considering the meta-analysis of diverse transcriptomics datasets and integrating gene expression profiles with biological networks are very limited.

Keller and co-workers (2008) studied gene expression profiles in eight experimental groups of lean and obese mice.

To read the rest of this article click here.

OMICS: A Journal of Integrative Biology integrates global high-throughput and systems approaches to 21st century science from “cell to society” – seen from a post-genomics perspective. The above article was first published in the September 2015 issue of OMICS: A Journal of Integrative Biology with the title “Tissue-Specific Molecular Biomarker Signatures of Type 2 Diabetes: An Integrative Analysis of Transcriptomics and Protein–Protein Interaction Data”. The views expressed here are those of the authors and are not necessarily those of OMICS: A Journal of Integrative Biology, Mary Ann Liebert, Inc., publishers, or their affiliates. No endorsement of any entity or technology is implied.

http://www.genengnews.com/insight-and-intelligence/tissue-specific-molecular-biomarker-signatures-of-type-2-diabetes/77900522/

Newly Identified Biochemical Pathway Could Be Target For Insulin Control

9/28/2015 Duke University

In the final event leading to the development of Type 2 diabetes, the pancreas loses its ability to secrete insulin and clear glucose from the blood. Preventing this breakdown in insulin secretion is a key goal in the fight to reduce the burden of a disease that afflicts an estimated 29 million people in the United States.

Now researchers at Duke Medicine and the University of Alberta are reporting the identification of a new biochemical pathway to control insulin secretion from islet beta cells in the pancreas, establishing a potential target for insulin control.

The study, published online Sept. 24 in the journal Cell Reports, results from a field of work called metabolomics, which uses mass spectrometry instruments to measure and trace intermediate molecules in key metabolic pathways of cells and tissues.

“The Duke group focused on metabolites in islet cells that changed in response to elevated external glucose concentrations,” said co-senior author Christopher B. Newgard, Ph.D., director of the Sarah W. Stedman Nutrition and Metabolism Center and the Duke Molecular Physiology Institute. “We found a strong increase in an intermediate in the purine/nucleotide metabolic pathway — known as adenylosuccinate, or S-AMP — in islets stimulated with glucose.”

Impairment of S-AMP production was shown to interfere with normal glucose-stimulated insulin secretion. The Duke and University of Alberta Diabetes Institute teams were also able to demonstrate that S-AMP is capable of rescuing impaired insulin secretion in islets from people with Type 2 diabetes.

Newgard said the collaborative effort between the Duke and Alberta teams also yielded a separate finding, reported online Sept. 21 in the Journal of Clinical Investigation, which describes another molecular pathway that could be a potential metabolic target for insulin control.

In that study, the research teams identified a process that works essentially like a dimmer switch to adjust how much or how little insulin is secreted when blood sugar increases. This dimmer switch appears to be broken in Type 2 diabetes, but the researchers found that its function can be restored.

“For the moment, we have two separate mechanisms, but with further study we may find that they are more connected,” Newgard said. “Whether they are independent, additive or synergistic is unknown, so we are eager to bring the two projects together to see where that may lead.”

The National Institutes of Health and the Canadian Institutes of Health Research funded the research.

Source: Duke University

http://www.biosciencetechnology.com/news/2015/09/newly-identified-biochemical-pathway-could-be-target-insulin-control?