Navigation Links
Blood sugar's manufacture limited by building blocks' supply

Researchers have discovered a factor that controls blood sugar's manufacture in a novel way: by limiting the supply of its building blocks. The findings are reported in the April issue of the journal Cell Metabolism, published by Cell Press.

The study found that mice deficient for KLF15, a member of the so-called Krüppel-like family of transcription factors, become severely lacking in the blood sugar glucose—a primary energy source for the body and the sole source for the brain—after a period of overnight fasting. The researchers traced that deficiency back to an inability to produce new glucose in the liver, a process known as gluconeogenesis, due to a defect in the processing of amino acids. Amino acids are the main ingredients of proteins and the source of a key substrate in blood sugar's production.

"Gluconeogenesis is a complicated process," said Mukesh K. Jain of Case Western Reserve University. "It fundamentally requires two big things: the building blocks and the [glucose-building] enzymes that make it all happen. A lot of previous work has focused on the enzymes."

"We've found the first defect [in glucose production] due to a loss of substrate," added Susan Gray of Brigham and Women's Hospital.

During fasting, the supply of glucose derived from food dries up, Gray explained. In response, the body first breaks down liver glycogen, the principal storage form of glucose. However, the body "goes through those stores overnight," she said.

Once the reserves are depleted, the body must rely on the synthesis of new glucose, primarily in the liver, to prevent a life-threatening shortage, a condition known as hypoglycemia. The de novo synthesis of glucose depends on the availability of a substrate molecule that comes from an amino acid.

The researchers found that mice with a targeted deletion of KLF15 display severe hypoglycemia after an overnight fast. They further found evidence that defective amino acid brea kdown promotes the development of fasting hypoglycemia in the mutant animals by limiting the availability of a glucose substrate called pyruvate.

Indeed, the mice had markedly reduced activity of genes that encode amino acid-degrading enzymes, the researchers showed. The mice also had a deficiency in the activity of an enzyme that converts the critical amino acid, called alanine, into pyruvate. Consistent with this observation, injection of pyruvate, but not alanine, rescued the mice from their fasting hypoglycemia.

The findings point to a novel form of control over glucose levels, the researchers said. Ultimately, this "window into glucose control" might also have implications for diabetes treatment—a condition characterized by high glucose concentrations, Gray said.

"Inhibiting KLF15 might prove beneficial in people with type II diabetes who have too much glucose, partly because the liver produces more than necessary," Jain said.

"Their glucose sensor is off. If you attenuate KLF15 in the liver, you might limit glucose production."

Gray said she plans to further explore the underlying mechanisms involved in KLF15's glucose regulation and see how increasing KLF15 levels affects blood sugar production. Meanwhile, Jain plans to further examine the transcription factor's function in other parts of the body where it is active, namely in skeletal and heart muscle.


'"/>

Source:Cell Press


Related biology news :

1. Placenta Is A Rich Source Of Blood Stem Cells
2. Infants With Rare Genetic Disease Saved by Cord Blood Stem Cells
3. White Blood Cell Waste Disposal System Plays Critical Regulatory Role
4. Mystery Blood Vessel Disorder Implicated In Mini Strokes
5. Infants with Rare Genetic Disease Saved By Cord Blood Stem Cells
6. Young Blood Revives Aging Muscles, Stanford Researchers Find
7. Stem Cells to Solve the Blood Shortage Problem?
8. Blood flow in brain takes a twist, affecting views of Alzheimers
9. Blood test predicts success of quitting smoking using the nicotine patch
10. Blood-compatible nanoscale materials possible using heparin
11. Blood transfusion-transmitted infections: A global perspective
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:2/14/2017)... WINSTON-SALEM, N.C. , Feb. 14, 2017  Wake ... FRY-shlog), M.D., as its new chief executive officer (CEO). ... succeeds CEO John D. McConnell , M.D., who ... new position at the Medical Center, after leading it ... oversee the full scope of Wake Forest Baptist,s academic ...
(Date:2/8/2017)... , Feb. 8, 2017 About Voice ... voice to match it against a stored voiceprint ... as pitch, cadence, and tone are compared to ... minimal hardware installation, as most PCs already have ... different transactions. Voice recognition biometrics are most likely ...
(Date:2/7/2017)... --  MedNet Solutions , an innovative SaaS-based eClinical technology ... is pleased to announce that the latest release of ... and award winning eClinical solution, is now available for ... a proven Software-as-a-Service (SaaS) clinical research technology platform that ... delivers an entire suite of eClinical tools to support ...
Breaking Biology News(10 mins):
(Date:2/22/2017)... ... February 22, 2017 , ... ... of Tom Perkins as European director. Operating from Pennside’s Zurich headquarters, Pennside Partners, ... , Perkins joins Pennside after more than a decade with leading market research ...
(Date:2/22/2017)... SILVER SPRING, Md. and RESEARCH TRIANGLE PARK, N.C., ... UTHR ) today announced its financial results ... 2016. "Our annual 2016 financial results ... billion and earnings exceeded $700 million," said Martine ... Officer. "These financial results strengthen our ability to ...
(Date:2/21/2017)... Inc. ("SQI" or the "Company") (TSX-V: SQD; OTCQX: SQIDF), today reported ... December 31, 2016. SQI is a ... develops and commercializes proprietary technologies and products for advanced multiplexed ... ... in fiscal 2016," said Andrew Morris , SQI,s President ...
(Date:2/21/2017)... ... February 21, 2017 , ... Vortex ... , a fully automated benchtop system for collecting intact circulating tumor cells (CTCs) ... at the Molecular Medicine Tri Conference (Tri-Con) Annual Meeting 2017 (February 19–24 San ...
Breaking Biology Technology: