CR reverses heart tendon glycation?

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Hi All,

See the pdf-available apparently only abstract for this paper seeming

to show that the glycation of tendon in the heart tissue by increased

glucose levels is a health risk that is alleviated by CR.

Monnier VM, Strauch C, Viswanathan A, Sell DR, Mc RJ.

Overexpression of GLUT4 in Muscle and Heart Leads to Increased

Cardiac Myosin Glycation and Early Death: Suppression by Caloric

Restriction.

Ann N Y Acad Sci. 2005 Jun;1043:916. No abstract available.

PMID: 16037345

Background. Caloric restriction (CR) prolongs life span by a

mechanism possibly involving the glucose-insulin axis and a decrease

in glycemia. To test this hypothesis, control (CON) and transgenic

(TG) mice overexpressing GLUT4 in peripheral and cardiac muscle (PNAS

90:11346-11350,1993) were fed ad libitum (CON-AL, TG-AL) or were 40%

calorie restricted (CON-CR, TG-CR) until spontaneous death. Survival

curves were determined. Mice were also sacrificed at 6, 12, and 30 mo

for assays of glycation (furosine) and glycoxidation markers of

glycemic damage (carboxymethyl-lysine, CML; carboxyethyl-lysine, CEL)

by GC/MS in isolated heart and muscle myosin, as well as tendon.

Total crosslinking was measured by tendon breaking time assay (TBT).

Results. Mean and maximum longevities were similar in CON and TG

mice, and were increased 25-30% by CR (P < 0.001) in both. However,

the death rate in TG-AL mice was initially higher than in other

groups. This was reflected by a 10x and 5x increase in cardiac myosin

glycation at 6 and 30 mo, respectively (P < 0.001), which was

suppressed by CR. CML and CEL were consistently increased in cardiac

tissue from TG-AL and suppressed by CR (P values variable). In

contrast, while CR suppressed myosin glycation at 30 mo in CON, it

did not suppress CEL and CML. In peripheral muscle, glycation and

glycemic damage were generally higher in TG mice, and CR tended to

suppress them in both CON and TG (p values variable) mice. Tendon

crosslinking was similar in CON and TG mice and suppressed by CR (P <

0.001). Surprisingly, while tendon glycation, a parameter of

glycemia, was suppressed 20-25% by CR (P < 0.001) in both CON and TG

mice, it was less than 10% lower in TG-AL vs. CON-AL mice.

Conclusions. Lifetime overexpression of GLUT4 in muscle results in a

small decrease in mean glycemia, as reflected by tendon glycation and

an accelerated death rate at midlife, which may be linked to

increased cardiac glycemic damage. These data point to the potential

danger of treating diabetes by forcing glucose entry into muscle,

especially the heart.