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Biomedical subjects

T P Shankar

Publications and source records attributed to T P Shankar.

7 recordsLinked to original sources
PubMed1988

Growth hormone and carbohydrate intolerance in cirrhosis.

Patients with cirrhosis of the liver often have insulin resistance and elevated circulating growth hormone levels. This study was undertaken (a) to evaluate glucose intolerance, insulin resistance and abnormal growth hormone secretion and (b) to determine if GH suppression improves insulin resistance. Glucose tolerance tests (GTT), intravenous insulin tolerance tests (IVITT), arginine stimulation tests (AST) and glucose clamp studies before and during GH suppression with somatostatin were performed in a group of patients with alcohol-induced liver cirrhosis. During GTT cirrhotic subjects had a 2-hour plasma glucose of 200 +/- 9.8 ng/dl (N = 14) compared to 128 +/- 8.0 ng/dl in normal controls (N = 15), P less than 0.001. Basal GH was elevated in cirrhotic patients and in response to arginine stimulation reached a peak of 17.0 +/- 5.4 ng/ml (N = 7), compared to a peak of 11.3 +/- 1.8 ng/ml in 5 normal controls (P = NS). During IVITT patients with cirrhosis had a glucose nadir of 60.0 +/- 4.0 mg/dl (N = 9), compared to 29.0 +/- 7.0 mg/dl in controls (N = 5), P less than 0.001. Peak GH levels during IVITT were not significantly different in cirrhotics and controls. Glucose utilization rates in 4 patients with cirrhosis of the liver before somatostatin mediated GH suppression was 3.1 +/- 0.5 mg/kg/min and 6.5 +/- 1.5 mg/kg/min during somatostatin infusion, P less than 0.025. We conclude that patients with alcohol induced cirrhosis have sustained GH elevations resulting in insulin resistance which improves after GH suppression.

Adult↗
PubMed1987

Insulin resistance and delayed clearance of peptide hormones in cirrhotic rat liver.

Clearance of porcine insulin, glucagon, and human growth hormone was measured in intact perfused cirrhotic and normal rat livers. Binding and degradation of 125I-insulin by hepatocytes isolated from cirrhotic and normal livers were also studied. The half-lives (t1/2) of immunoreactive insulin and glucagon were 14.0 +/- 3.1 and 9.6 +/- 2.1 min in normal livers and 26.0 +/- 6.1 and 25.0 +/- 7.1 min in cirrhotic livers (P less than 0.001). Insulin binding and degradation by hepatocytes from control and cirrhotic livers showed no significant differences. Intraportal insulin infusion in perfusion studies suppressed glucagon-stimulated increases in glucose output from control livers but failed to suppress glucose production by cirrhotic livers, suggesting the presence of hepatic insulin resistance in cirrhosis. Impaired clearance of insulin and glucagon by the intact cirrhotic liver and normal binding and degradation of insulin by isolated hepatocytes suggest that factors such as intrahepatic fibrosis and shunting and postbinding defects may be responsible for the impaired hormone clearance and hepatic insulin resistance.

Animals↗
PubMed1986

Elevated growth hormone levels and insulin resistance in patients with cirrhosis of the liver.

Carbohydrate intolerance is frequently seen in patients with hepatic cirrhosis. To study the role of the counter regulatory hormones, glucagon, cortisol and growth hormone in this disease, these hormones were measured in 11 patients with hepatic cirrhosis and six controls during a 4-hour oral glucose tolerance test (OGTT) and in five normal and cirrhotic subjects during steady-state plasma insulin and glucose concentrations (SSPGI) achieved with the euglycemic clamp technique. Fasting plasma glucose was 103 +/- 4.3 mg/dl in cirrhotics and 88 +/- 3.3 mg/dl in controls (p less than 0.001). Immunoreactive insulin (IRI) was 24.3 microU/ml in cirrhotics and 12.7 +/- 2.2 microU/ml in controls (p less than 0.001); immunoreactive glucagon (IRG) was 263 +/- 30 pg/ml in cirrhotics and 122 +/- 17.5 pg/ml in controls (p less than 0.001); serum growth hormone (GH) was 4.4 +/- 0.9 ng/ml in cirrhotics and 0.5 +/- 0.1 ng/ml in controls (p less than 0.001). During OGTT, the 2-hour glucose concentration was 201 +/- 9.7 mg/dl in cirrhotic subjects and 147 +/- 10.0 mg/dl in controls (p less than 0.001). IRG levels were suppressed by 20% of basal values in patients with cirrhosis, while controls showed 10% suppression after an oral glucose load. At 60 minutes, the serum GH was 14.7 +/- 3.9 ng/ml in cirrhotics and 0.3 +/- 0.1 ng/ml in controls (p less than 0.001). The normal suppressive effect of hyperglycemia on GH secretion in controls was sharply contrasted by a paradoxical elevation of serum GH in the cirrhotic group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Cyclic AMP phosphodiesterase in diabetes. Effect of glyburide.

Low-Michaelis constant cAMP phosphodiesterase (PDE; EC3.1.4.C) activity is inhibited in tissues of rats with type I ketosis-prone diabetes and is restored to normal by insulin treatment. To determine whether the oral hypoglycemic agent glyburide affected tissue cAMP PDE activity in non-insulin-dependent oral agent-treatable diabetes, cAMP PDE activity was measured in the liver and fat of animals rendered diabetic by low-dose streptozocin (STZ-DM) and treated for 3 wk with oral glyburide (360 micrograms/kg). The results were compared with PDE activity in the liver and fat of untreated STZ-DM and normal control rats. At the time of death, low-Km cAMP PDE activity [as maximum velocity (Vmax)] in STZ-DM rats was decreased to 66% of control values in the liver and to 65% in fat (P less than .001). PDE activity was restored toward normal by glyburide treatment: 91% in the liver (P less than .01) and 80% in fat (P less than .05). Calmodulin and calmodulin-like activity (PDE-activator activity) in the liver and fat was decreased in diabetes and restored toward normal after glyburide treatment (P less than .05). These data demonstrate that oral agents as well as insulin can restore the activity of cAMP PDE in the low-dose STZ-DM model, which is in some ways similar to type II diabetes.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1983

Glucagon degradation by human mononuclear cells.

Degradation of 125I-iodoglucagon by human mononuclear cell preparations including one containing 18%-27% monocytes, one consisting of 97% pure monocytes and one consisting of 98% lymphocytes was examined. Intact cells were incubated with 125I-iodoglucagon and degradation assessed by measuring an increase in trichloroacetic acid soluble products or in non-immunoprecipitable products. The preparation consisting of intact lymphocytes did not degrade glucagon. Glucagon was degraded by preparations containing monocytes and this degradation increased with time. No difference between monocyte degradation as measured by trichloroacetic acid or immunoprecipitation was found. Degradation by intact monocytes and by mononuclear homogenates increased sixfold from 4 degrees C to 37 degrees C. Subcellular fractionation demonstrated that the majority of the neutral glucagon degrading activity was in the 100,000 g supernatant (cytosol). Kinetic analyses gave Km values of 1.1 x 10(-5) mol/l, 7.5 x 10(-6) mol/l, and 1.2 x 10(-5) mol/l for glucagon degradation by intact mononuclear cells, homogenates, and cytosol, respectively. Inhibitor studies indicated a sulphydryl dependent enzyme was involved in glucagon degradation by both intact cells and cytosol. The monocyte appeared to be the cell responsible for degradation of glucagon by mononuclear cell preparations. The degradation of glucagon under physiological conditions by intact monocytes was mediated by a neutral proteolytic enzyme, primarily localized in the cytosol.

Cell Nucleus↗
PubMed1983

Studies of glucose intolerance in cirrhosis of the liver.

Patients with hepatic cirrhosis often have demonstrable glucose intolerance. We studied 21 patients with cirrhosis of the liver. Oral glucose tolerance tests (OGTT), intravenous arginine stimulation tests (IVAST), and intravenous insulin tolerance tests (IVITT) were performed, and timed blood samples were obtained for the assay of glucose immunoreactive insulin (IRI), C-peptide (C-P), and immunoreactive glucagon (IRG). The 125I-insulin binding to circulating monocytes was studied in some of the patients. All results were compared to those of similar studies performed on healthy controls. During OGTT significant glucose intolerance was demonstrable in the patients with cirrhosis (2 hr plasma glucose 198.8 +/- 14.3 mg/dl in cirrhosis and 116.4 +/- 4.2 in controls; p less than 0.001). Two-hour plasma IRI, C-P, and IRG were significantly higher in the cirrhotic patients than in controls (p less than 0.001; less than 0.001; less than 0.025). In response to IVAST, the patients with cirrhosis showed a greater first-phase insulin secretion and controls had a slightly better second-phase insulin release. Plasma IRG rose from a basal value of 446 pg/ml to 1100 in the patients with cirrhosis and from 171 pg/ml to 494 in controls. After intravenous insulin administration, there was only a 40% decline in plasma glucose concentration from basal values in the patients with cirrhosis whereas the controls showed a 60% decline, demonstrating that the patients with cirrhosis had significant insulin resistance. Moreover, the half-life of insulin was prolonged in the patients with cirrhosis (t 1/2 = 15.5 min in cirrhosis and 10.3 in controls; p less than 0.001); and the ratio of C-P to insulin during OGTT was also reduced, indicating that the patients with cirrhosis have reduced hepatic clearance of insulin. The specific binding of 125I-insulin to circulating monocytes was 2.7% in cirrhosis, 2% in obese controls, and 4% in lean controls. There was a significant negative correlation between the fasting plasma insulin values and the specific binding of insulin. In conclusion, patients with hepatic cirrhosis have significant glucose intolerance characterized by hyperinsulinemia, hyperglucagonemia, insulin resistance, and down-regulation of insulin receptors. Although hyperinsulinemia is probably caused by reduced hepatic clearance of insulin, hyperglucagonemia is primarily due to increased pancreatic secretion.

Adult↗