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type 2 diabetes

Tuesday 23 September 2003

Type 2 diabetes is a polygenic disorder characterized by multiple biochemical defects including transcriptional, translational, and posttranslational abnormalities. Although major progress has been made in elucidation of factors at the transcriptional and posttranslational levels, defects at the translational level remain elusive.

Insulin resistance

The insulin resistance of type 2 diabetes appears to be caused in part by the presence of high levels of lipids in cells such as skeletal muscle where this would not normally be found. The presence of excess lipid stores in skeletal muscle cells interferes with energy metabolism, impairing glucose oxidation and insulin response.

Skeletal muscle is one of the primary glucose-consuming tissues, giving it a central role in insulin resistance. The increased risk of diabetes associated with obesity may be caused by increased lipid deposits in skeletal muscle and liver, creating insulin resistance.

Translational anomalies

 see translation diseases

Susceptibility loci

 5q34-q35.2 (12851856)
 calpain-10 variation

Videos

 Type 2 Diabetes mellitus by Washington Deceit

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 Diabetes

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References

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 Frayling TM. Genome-wide association studies provide new insights into type 2 diabetes aetiology. Nat Rev Genet. 2007 Sep;8(9):657-62. PMID: 17703236

 Yki-Jarvinen H, Westerbacka J. The fatty liver and insulin resistance. Curr Mol Med. 2005 May;5(3):287-95. PMID: 15892648

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 Taskinen MR. Type 2 diabetes as a lipid disorder. Curr Mol Med. 2005 May;5(3):297-308. PMID: 15892649

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 Ashcroft F, Rorsman P. Type 2 diabetes mellitus: not quite exciting enough? Hum Mol Genet. 2004 Apr 1;13 Spec No 1:R21-31. PMID: 14734629

 McCarthy MI. Progress in defining the molecular basis of type 2 diabetes mellitus through susceptibility-gene identification. Hum Mol Genet. 2004 Apr 1;13 Spec No 1:R33-41. PMID: 14722160

 Cederberg A, Enerback S. Insulin resistance and type 2 diabetes—an adipocentric view. Curr Mol Med. 2003 Mar;3(2):107-25. PMID: 12630558

 Lingohr MK, Buettner R, Rhodes CJ. Pancreatic beta-cell growth and survival—a role in obesity-linked type 2 diabetes? Trends Mol Med. 2002 Aug;8(8):375-84. PMID: 12127723

 Cox NJ. Challenges in identifying genetic variation affecting susceptibility to type 2 diabetes: examples from studies of the calpain-10 gene. Hum Mol Genet. 2001 Oct 1;10(20):2301-5. PMID: 11673414

 Sone H, Suzuki H, Takahashi A, Yamada N. Disease model: hyperinsulinemia and insulin resistance. Part A-targeted disruption of insulin signaling or glucose transport. Trends Mol Med. 2001 Jul;7(7):320-2. PMID: 11425641

 Sone H, Takahashi A, Iida K, Yamada N. Disease model: hyperinsulinemia and insulin resistance. Part B—polygenic and other animal models. Trends Mol Med. 2001 Aug;7(8):373-6. PMID: 11516999

 Hoppener JW, Ahren B, Lips CJ. Islet amyloid and type 2 diabetes mellitus. N Engl J Med. 2000 Aug 10;343(6):411-9. PMID: 10933741