Feb 2011
IRIG: Update on mitochondrial dysfunction in insulin resistance
02/23/2011 23:19
Mitochondrial
dysfunction is observed in insulin resistance and
type 2 diabetes. It is proposed as a mechanism for
the pathogenesis of insulin resistance in 2004. In
the past few years, research on this topic is very
active and huge progress has been made. Current
literature suggests following two points: (I)
mitochondrial dysfunction is a protection mechanism
against insulin resistance; (II) mitochondrial
inhibition is able to improve insulin
sensitivity. The two points are supported by
following literature: (A) Mitochondrial
dysfunction is a result of insulin resistance in most
model systems as documented in a review article
(1).
(B) All of the clinically approved drugs for insulin
sensitization are able to inhibit mitochondrial
function. Inhibition of mitochondrial function
by Berberine leads to insulin sensitization through
AMPK activation (2).
Berberine is an herbal insulin sensitizer that is
wildly used in China. This activity of
berberine was confirmed in a later study for AMPK
activation, in which berberine was tested together
with TZDs and metformin for inhibition of
mitochondrial function (3).
In genetic study, inhibition of mitochondrial
function by transgenic modification leads to
protection of mice from insulin resistance
(4).
Reference:
1. Pagel-Langenickel I, Bao J, Pang L, Sack MN: The role of mitochondria in the pathophysiology of skeletal muscle insulin resistance. Endocr Rev 2010;31:25-51
2. Yin J, Gao Z, Liu D, Liu Z, Ye J: Berberine Improves Glucose Metabolism through Induction of Glycolysis. Am J Physiol Endocrinol Metab 2008;294:E148-E156
3. Hawley SA, Ross FA, Chevtzoff C, Green KA, Evans A, Fogarty S, Towler MC, Brown LJ, Ogunbayo OA, Evans AM, Hardie DG: Use of cells expressing gamma subunit variants to identify diverse mechanisms of AMPK activation. Cell Metab 2010;11:554-565
4. Li J, Romestaing C, Han X, Li Y, Hao X, Wu Y, Sun C, Liu X, Jefferson LS, Xiong J, Lanoue KF, Chang Z, Lynch CJ, Wang H, Shi Y: Cardiolipin remodeling by ALCAT1 links oxidative stress and mitochondrial dysfunction to obesity. Cell Metab 2010;12:154-165
By Jim --------------------------------
Jianping Ye, M.D.
Professor of Molecular Biology
Antioxidant and Gene Regulation Lab
PBRC/LSU
E-mail: yej@pbrc.edu
Phone: (225) 763-3163
Reference:
1. Pagel-Langenickel I, Bao J, Pang L, Sack MN: The role of mitochondria in the pathophysiology of skeletal muscle insulin resistance. Endocr Rev 2010;31:25-51
2. Yin J, Gao Z, Liu D, Liu Z, Ye J: Berberine Improves Glucose Metabolism through Induction of Glycolysis. Am J Physiol Endocrinol Metab 2008;294:E148-E156
3. Hawley SA, Ross FA, Chevtzoff C, Green KA, Evans A, Fogarty S, Towler MC, Brown LJ, Ogunbayo OA, Evans AM, Hardie DG: Use of cells expressing gamma subunit variants to identify diverse mechanisms of AMPK activation. Cell Metab 2010;11:554-565
4. Li J, Romestaing C, Han X, Li Y, Hao X, Wu Y, Sun C, Liu X, Jefferson LS, Xiong J, Lanoue KF, Chang Z, Lynch CJ, Wang H, Shi Y: Cardiolipin remodeling by ALCAT1 links oxidative stress and mitochondrial dysfunction to obesity. Cell Metab 2010;12:154-165
By Jim --------------------------------
Jianping Ye, M.D.
Professor of Molecular Biology
Antioxidant and Gene Regulation Lab
PBRC/LSU
E-mail: yej@pbrc.edu
Phone: (225) 763-3163
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