Biomedical subjects

D Antwi

Publications and source records attributed to D Antwi.

3 recordsLinked to original sources

PubMed1988

Regulation of glycogen synthase in muscle and adipose tissue during fasting and refeeding.

Using immunoblot analysis, we examined the electrophoretic mobility of glycogen synthase from rat skeletal muscle and adipose tissue. Extracts from muscle freeze clamped in situ contained at least three forms of synthase with different electrophoretic mobilities. Extracts from adipose tissue also contained multiple forms but lacked the form with greatest mobility found in the muscle extracts. Phosphorylation at multiple sites of glycogen synthase is known to deactivate the enzyme and retard its electrophoretic mobility in sodium dodecyl sulfate gels. These results suggest that there is very little or no dephosphorylated glycogen synthase in adipose tissue and that phosphorylated forms of glycogen synthase synthesize adipose tissue glycogen. Relative to control, it is known that fasting decreases and refeeding increases glucose incorporation into glycogen in rat epididymal adipose tissue but not skeletal muscle incubated in vitro in the presence of insulin. Fasting did not change the electrophoretic pattern of muscle synthase but decreased the relative amount of adipose tissue forms with greater mobility. Refeeding increased above control the relative amount of adipose tissue synthase with greater mobility. These results indicate that changes in the phosphorylations that retard mobility contribute to the effects of fasting and refeeding on adipose tissue glycogen metabolism.

Adipose Tissue↗

PubMed1986

Effect of ciglitazone on glucose uptake and insulin sensitivity in skeletal muscle of the obese (ob/ob) mouse: distinct insulin and glucocorticoid effects.

The oral hypoglycemic agent, ciglitazone, (5-[4-(1-methylcyclohexylmethoxy)benzyl]-thiazolidine-2,4-dione), was fed for nine days to genetically obese (ob/ob) mice aged 5 to 6 weeks. This treatment resulted in a lowering of plasma glucose and circulating insulin levels, but did not cause a fall in plasma corticosterone levels. Basal 2-deoxy-D-glucose uptake by the perfused hindquarters of ob/ob mice was unchanged by ciglitazone feeding. In the presence of 0.1 mU/mL insulin in the perfusion medium, there was a significant increase in the uptake rate of 2-deoxy-D-glucose by the skeletal muscle of ciglitazone-treated ob/ob mice, while there was no insulin effect in untreated ob/ob mice. Insulin at a concentration of 1 mU/mL caused a further stimulation of 2-deoxy-D-glucose transport. However, this response was significantly lower than the maximal stimulation in lean mice. Ciglitazone feeding did not have any effect on [5-3H]-glucose metabolism by the perfused muscle which remained subnormal, suggesting that the posttransport metabolism of glucose was limited by substrate availability. In the perfused mouse liver, net [14C]-glucose production from [14C]-lactate was unchanged by ciglitazone treatment while gluconeogenesis from [14C]-alanine was reduced. These findings show that ciglitazone produces its hypoglycemic effect by improving the insulin sensitivity in skeletal muscle, as others have reported in the adipose tissue. The presence of elevated plasma levels of corticosterone and lower levels of insulin in ciglitazone-treated ob/ob mice suggests that the adrenal glucocorticoids are responsible for the basal defects in glucose transport and the hyperinsulinemia is responsible for the insulin insensitivity.

Adrenal Cortex↗

PubMed1985

L-type glycogen synthase. Tissue distribution and electrophoretic mobility.

We previously reported (Kaslow, H.R., and Lesikar, D.D.FEBS Lett. (1984) 172, 294-298) the generation of antisera against rat skeletal muscle glycogen synthase. Using immunoblot analysis, the antisera recognized the enzyme in crude extracts from rat skeletal muscle, heart, fat, kidney, and brain, but not liver. These results suggested that there are at least two isozymes of glycogen synthase, and that most tissues contain a form similar or identical to the skeletal muscle type, referred to as "M-type" glycogen synthase. We have now used an antiserum specific for the enzyme from liver, termed "L-type" glycogen synthase, to study its distribution and electrophoretic mobility. Immunoblot analysis using this antiserum indicates that L-type glycogen synthase is found in liver, but not skeletal muscle, heart, fat, kidney, or brain. In sodium dodecyl sulfate-polyacrylamide gels of crude liver extracts prepared with protease inhibitors, rat L-type synthase was detected with electrophoretic mobility Mapp = 85,000. In contrast, the M-type enzyme in crude skeletal muscle extracts with protease inhibitors was detected with Mapp = 86,000 and 89,000. During purification of L-type synthase, apparent proteolysis can generate forms with increased electrophoretic mobility (Mapp = 75,000), still recognized by the antiserum. These M-type and L-type antisera did not recognize a protein with Mapp greater than phosphorylase. The anti-rat L-type antisera recognized glycogen synthase in blots of crude extracts of rabbit liver, but with Mapp = 88,000, a value 3,000 greater than that found for the rat liver enzyme. The anti-rat M-type antisera failed to recognize the enzyme in blots of crude extracts of rabbit muscle. Thus, in both muscle and liver, the corresponding rat and rabbit enzymes are structurally different. Because the differences described above persist after resolving these proteins by denaturing sodium dodecyl sulfate electrophoresis, these differences reside in the structure of the proteins themselves, not in some factor bound to the protein in crude extracts.

Animals↗