Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 115, Issue 12, Pages 3587-3593Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI25151
Keywords
-
Categories
Funding
- NCRR NIH HHS [M01 RR000125, M01 RR-00125] Funding Source: Medline
- NIA NIH HHS [R01 AG-23686, R01 AG023686] Funding Source: Medline
- NIDDK NIH HHS [P30 DK-45735, R01 DK040936, P30 DK045735, R01 DK-063192, P01 DK068229, P01 DK-68229, R01 DK-49230, R01 DK049230] Funding Source: Medline
Ask authors/readers for more resources
To further explore the nature of the mitochondrial dysfunction and insulin resistance that occur in the muscle of young, lean, normoglycemic, insulin-resistant offspring of parents with type 2 diabetes (IR offspring), we measured mitochondrial. content by electron microscopy and insulin signaling in muscle biopsy samples obtained from these individuals before and during a hyperinsulinemic-euglycemic clamp. The rate of insulin-stimulated muscle glucose uptake was approximately 60% lower in the IR offspring than the control subjects and was associated with an approximately 60% increase in the intramyocellular lipid content as assessed by H-1 magnetic resonance spectroscopy. Muscle mitochondrial density was 38% lower in the IR offspring. These changes were associated with a 50% increase in IRS-1 Ser312 and IRS-1 Ser636 phosphorylation and an approximately 60% reduction in insulin-stimulated Akt activation in the IR offspring. These data provide new insights into the earliest defects that may be responsible for the development of type 2 diabetes and support the hypothesis that reductions in mitochondrial content result in decreased mitochondrial function, which predisposes IR offspring to intramyocellular lipid accumulation, which in turn activates a serine kinase cascade that leads to defects in insulin signaling and action in muscle.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available