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Biomedical subjects

A S Reddi

Publications and source records attributed to A S Reddi.

At least 55 records · Page 3Linked to original sources
PubMed1988

Collagen metabolism in the myocardium of normal and diabetic rats.

Myocardial collagen and total protein synthesis were studied in normal, diabetic, and insulin-treated diabetic rats after a single intraperitoneal injection of L-[2,3-3H]proline as a radioisotopic precursor. The incorporation of tritiated proline into myocardial protein was regarded as a measure of total protein synthesis and the incorporation into hydroxyproline as indicative of myocardial collagen synthesis. Both total protein and collagen synthesis were found to be significantly lower in diabetic rats. This was associated with decreased degradation of both total protein and collagen in diabetic rats, as suggested by prolonged turnover times. Collagen content was also found to be increased in diabetic myocardium. Early insulin therapy with normalization of blood sugars in diabetic rats returned myocardial collagen metabolism to normal. This suggests that maintenance of euglycemia in diabetic rats is necessary to prevent abnormal myocardial collagen metabolism.

Animals↗
PubMed1988

Delay of progression of diabetic microangiopathy.

Three muscle biopsies were performed in 53 overt type II diabetics over a period of approximately 2 years. At baseline, 21 (40%) had an abnormally increased capillary basement membrane width in muscle. Thirty-five subjects received glipizide and 18, placebo. At baseline, no statistically significant difference was found in the muscle capillary basement membrane width between the two groups (P = NS). In the subjects receiving placebo, the mean width of the muscle capillary basement membrane increased (P = NS), but in those receiving glipizide, the mean decreased from 193 +/- 13 nm (SEM) to 161 +/- 10 nm (P = .02). Fasting plasma glucose and glycosylated hemoglobin A1 significantly decreased (P less than .001) after two years in those receiving glipizide. In 15 subjects, mean glycosylated hemoglobin A1 reached the normal range, and mean muscle capillary basement membrane width decreased to a level close to that found in subjects without diabetes (P = NS). Determinations of enzyme activities involved in the synthesis and degradation of glycoproteins revealed a 2-year significant decrease of muscle glucosyltransferase (synthesis) activity (P less than .01) in the glipizide-treated subjects as opposed to a significant increase (P less than .001) in those receiving placebo. Muscle N-acetyl-beta-glucosaminidase activity (degradation) was statistically increased (P less than .001) in those subjects taking glipizide, but decreased in those taking placebo (P less than .001).

Acetylglucosaminidase↗
PubMed1988

Glomerular basement membrane collagen synthesis rates in normal and diabetic rats.

Glomerular basement membrane (GBM) protein and collagen synthesis rates were studied in normal and streptozotocin diabetic rats, using L-(2,3,3H)-proline as a radioactive precursor. The incorporation of tritiated proline into GMB proline was regarded as a measure of total protein synthesis and the incorporation into hydroxyproline as indicative of collagen synthesis. Total GBM protein and collagen synthesis rates were calculated from the simultaneous measurements of specific activities in the precursor (tissue-free) and protein-bound (GBM proline and hydroxyproline) pools. The results suggest that diabetic rats synthesized GBM protein and collagen at the rate of 1.90 and 0.61% per h, respectively, compared to 1.07 and 0.38% per h in normal rats. These data are consistent with our previous findings of increased GBM protein and collagen synthesis in streptozotocin diabetic rats.

Animals↗
PubMed1986

Riboflavin nutritional status and flavoprotein enzymes in streptozotocin-diabetic rats.

Riboflavin nutritional status was assessed on the basis of activity coefficients of glutathione reductase in erythrocyte hemolysates of normal and streptozotocin-diabetic rats. Activity coefficient values higher than 1.3 were regarded as evidence of riboflavin deficiency. All diabetic animals were found to be riboflavin-deficient, with activity coefficient values of 1.47-2.11. Treatment of diabetic rats with either insulin or riboflavin returned their activity coefficients to normal. Rats fed a restricted diet had normal activity coefficient values. The erythrocyte glutathione reductase activity was significantly lower in diabetic rats, and the augmentation of enzyme activity in the presence of flavin-adenine dinucleotide (FAD) was 72% compared to 16% in normal rats. Hepatic activities of glutathione reductase and succinate dehydrogenase, both FAD-containing enzymes, were significantly lower in diabetic than in normal rats. Like activity coefficient values, all enzyme activities were normalized after insulin or riboflavin treatments. These data suggest that insulin and riboflavin enhance the synthesis of erythrocyte and hepatic FAD. The results of the present study suggest that experimental diabetes causes riboflavin deficiency, which in turn decreases erythrocyte and hepatic flavoprotein enzyme activities. These changes can be corrected for by either insulin or riboflavin. The pathogenesis of riboflavin deficiency in diabetes mellitus is not clearly understood. The data of the present study provide evidence in addition to the previous findings of an increased prevalence of riboflavin deficiency in genetically diabetic KK mice.

Animals↗
PubMed1986

Metabolism of glomerular basement membrane in short- and long-term streptozotocin diabetic rats.

The synthesis of glomerular basement membrane (GBM) total protein and collagen was assessed by two methods in vivo in normal and streptozotocin diabetic rats 4-6 weeks and 42-44 weeks after onset of hyperglycaemia, using L-[2, 3, 3H] proline as a radioactive precursor. The incorporation of tritiated proline into GBM hydroxyproline was used as a measure of collagen synthesis and that into proline as total protein synthesis. The basement membrane fractions from both short- and long-term diabetic rats attained much higher proline and hydroxyproline specific activities compared to normal GBM proline and hydroxyproline specific activities. Early insulin therapy with normalization of blood sugar levels in short-term (4-6 weeks) diabetic rats returned the abnormal increases in GBM total protein and collagen synthesis to normal. By contrast, poor glycaemic control with insulin did not prevent the increases in GBM protein synthesis. The results of the present study suggest that overall enhancement of GBM protein synthesis occurs in both short- and long-term streptozotocin diabetes. Early insulin therapy with normalization of blood sugar levels prevents this increase in GBM protein synthesis. Poor glycaemic control had no effect on abnormal GBM protein synthesis. This may be of potential significance in view of preventing chronic diabetic microvascular complications such as nephropathy.

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PubMed1985

Metabolism of glomerular basement membrane in normal, hypophysectomized, and growth-hormone-treated diabetic rats.

The in vivo synthesis of the renal glomerular basement membrane (GBM) collagen was studied in normal, hypophysectomized (hypox), diabetic, and growth-hormone (GH)-treated diabetic rats, using tritiated proline (L[2,3,3H]proline) as a radioisotopic precursor. After the injection of tritiated proline, all groups of rats were sacrificed at various time intervals and the specific activities of proline and hydroxyproline of GBM were determined, the latter being used as a measure of GBM collagen synthesis. A significant decrease in both proline and hydroxyproline specific activities were observed in GBM of hypox rats at all periods of study. Administration of GH to hypox rats returned the GBM collagen synthesis to normal. Diabetic GBM had higher proline and hydroxyproline specific activities when compared to normal rats. Treatment of diabetic rats with GH for 10 days further increased both proline and hydroxyproline specific activities when compared either to diabetic or normal rats treated with GH. The activity of glucosyltransferase, an enzyme involved in the biosynthesis of the disaccharide unit of GBM collagen was found to be decreased in glomeruli of hypox rats. In contrast, the activity of N-acetyl-beta-glucosaminidase, a glycoprotein-degrading enzyme, was found to be significantly increased in hypox rats. GH treatment restored both enzyme activities to normal. The results of the present study show that GBM collagen synthesis is decreased in hypox rats and increased in diabetic rats. GH treatment not only normalized GBM collagen synthesis in hypox rats but also caused significant increase in diabetic rats. This suggests that the renal GBM metabolism is influenced by GH, and this may be of particular significance in view of GH involvement in diabetic microvascular complications.

Acetylglucosaminidase↗
PubMed1985

Collagen metabolism in the retina of normal and diabetic rats.

Glucosyltransferase, an enzyme involved in the synthesis of the carbohydrate portion of basement membranes and collagens, and collagen content were determined in the retina of normal and streptozotocin diabetic rats. No significant difference in glucosyltransferase activity was found at 4 weeks of diabetes. However, the enzyme activity was significantly increased in diabetic rats 12 and 48 weeks following the induction of diabetes. Similarly, a significant increase in collagen content was observed in diabetic retinas after 12 weeks of diabetes. Electron microscopy showed marked thickening of the retinal capillary basement membrane in long-term diabetic (48 weeks) rats. The data suggest that enhanced collagen synthesis and deposition occurs in the retina of diabetic rats, and with duration of diabetes this may result in thickening of the capillary basement membrane. These results are compatible with previously reported increases in kidney glucosyltransferase, collagen synthesis and thickening of the capillary basement membrane in diabetic rats.

Animals↗
PubMed1979

Glucosyltransferase activity in kidney fractions of normal and streptozotocin-diabetic rats.

Glucosyltransferase (UDPglucose: galactosylhydroxylysine-basement membrane glucosyltransferase), an enzyme specifically involved in collagen synthesis, was measured in various kidney fractions of normal, diabetic and underfed rats, using as basis the incorporation of radioactivity into protein during incubation with UDP[U-14C]glucose and alkali-soluble fetal calf-skin collagen. Three criteria of enzyme activity were compared: A, total radioactivity of the washed protein precipitate; B, this figure minus activity incorporated in the absence of the collagen acceptor; and C, radioactivity incorporated into the mixed amino acid fraction, collected by elution with dilute NH4OH from a Dowex 50 resin column after alkaline hydrolysis of the protein. Method A was found satisfactory using whole medulla or isolated glomeruli, since the average proportions of total protein radioactivity recovered in the NH3 fraction were 0.81 and 0.87, respectively, and the deviations were small. There was a larger and variable proportion of nonspecific incorporation using whole cortex. Incubation of a control set of sample without added collagen was found to be unnecessary (Method B). Per mg protein, medulla and glomeruli had more enzyme than did whole cortex. In diabetes, activity was enhanced in the 10,000 X g supernatant fraction of cortex, as previously reported. However, the increase associated with diabetes was even more consistent in the medulla, averaging 3-fold in the 10,000 X g pellet fraction. No increase was found in isolated glomeruli in diabetes. Also, no increase was seen in the kidneys of non-diabetic rats with body weight similar to that of the diabetics.

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