Molecular reductions in glucokinase activity increase counter-regulatory responses to hypoglycemia in mice and humans with diabetes.

Molecular Metabolism
Ali J ChakeraM L Evans

Abstract

Appropriate glucose levels are essential for survival; thus, the detection and correction of low blood glucose is of paramount importance. Hypoglycemia prompts an integrated response involving reduction in insulin release and secretion of key counter-regulatory hormones glucagon and epinephrine that together promote endogenous glucose production to restore normoglycemia. However, specifically how this response is orchestrated remains to be fully clarified. The low affinity hexokinase glucokinase is found in glucose-sensing cells involved in glucose homeostasis including pancreatic β-cells and in certain brain areas. Here, we aimed to examine the role of glucokinase in triggering counter-regulatory hormonal responses to hypoglycemia, hypothesizing that reduced glucokinase activity would lead to increased and/or earlier triggering of responses. Hyperinsulinemic glucose clamps were performed to examine counter-regulatory responses to controlled hypoglycemic challenges created in humans with monogenic diabetes resulting from heterozygous glucokinase mutations (GCK-MODY). To examine the relative importance of glucokinase in different sensing areas, we then examined responses to clamped hypoglycemia in mice with molecularly defined d...Continue Reading

Citations

Jan 5, 2019·Endocrinology, Diabetes & Metabolism Case Reports·Aoife GarrahyMaria M Byrne
Jan 29, 2019·Endocrine Reviews·Sarah StanleyElizabeth R Seaquist
Jul 23, 2019·Journal of Neuroendocrinology·Pamela R HirschbergVanessa H Routh
Feb 20, 2020·The New England Journal of Medicine·Miriam S UdlerChristina A Austin-Tse
Sep 8, 2020·Diabetologia·Chelsea L FaberGregory J Morton
Oct 13, 2020·Diabetologia·Kimberly M AlongeMichael W Schwartz
Mar 23, 2020·Environmental Toxicology and Pharmacology·Muhammad Sajid Hamid AkashKanwal Rehman
Apr 3, 2021·Critical Reviews in Food Science and Nutrition·Giovanna MuscogiuriAnnamaria Colao
Nov 26, 2020·Metabolism Open·Toyin Mohammed SalmanSheu Oluwadare Sulaiman
Jan 7, 2022·Annual Review of Pharmacology and Toxicology·Zaman MirzadehMichael W Schwartz

❮ Previous
Next ❯

Methods Mentioned

BETA
ELISA
PCR

Software Mentioned

GraphPad
ARRIVE
GraphPad Prism

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.