Clarification of the molecular mechanism on the impaired glucose metabolism induced by heme deficiency

2015 Fiscal Year Final Research Report

• Project/Area Number: 25670158
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: Yamagata University
• Principal Investigator: Nakajima Osamu 山形大学, 医学部, 教授 (80312841)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 糖尿病 / 糖代謝異常 / ヘム / 5-アミノレブリン酸 / 5‐アミノレブリン酸合成酵素 / 耐糖能異常 / グリコーゲン / 糖尿病治療

Outline of Final Research Achievements

In vertebrates, the initial step in heme biosynthesis is the production of 5-aminolevulinic acid (ALA) by ALA synthase (ALAS). The ALAS1 gene encodes a ubiquitously expressed isozyme. Mice heterozygous null for ALAS1 (ALAS1+/-s) experience mitochondrial dysfunction (MD), impaired glucose tolerance (IGT) and insulin resistance (IR) past 20-weeks of age (aged-ALAS1+/-s). IGT/IR in aged-ALAS1+/-s was remedied by the oral administration of ALA for 1-week. By contrast, MD required 6-weeks of ALA-administration before improvements could be observed, indicating the IGT/IR phenotype is not due to MD. Aged-ALAS1+/-s showed impaired glycogen metabolism (IGyM) in skeletal muscle (SM)/liver and data indicate a defect in de novo glycogen synthesis that could account for the IGT/IR phenotype. Together, our data reveals an unexpected metabolic link between heme and glucose metabolism.

Free Research Field

分子生物学