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Biomedical subjects

L Susheela

Publications and source records attributed to L Susheela.

17 recordsLinked to original sources

Abnormalities in erythrocyte insulin binding in offspring of conjugal non-insulin-dependent diabetic parents.

Insulin binding to erythrocyte insulin receptors was studied in 23 offspring (13 men and 10 women) born of conjugal diabetic parents having type 2 diabetes. Nine of the offspring were obese and 14 were non-obese, but all had normal glucose tolerance. Twenty-three age-, sex- and weight-matched non-diabetic subjects without a family history of diabetes were studied as controls. In the non-obese offspring mean basal plasma immunoreactive insulin (IRI) was elevated (P less than 0.01), but the mean stimulated IRI showed no change in comparison to that of controls. In the obese offspring mean basal plasma IRI was similar, but the mean stimulated IRI was lower than that of obese controls (P less than 0.01). Mean specific insulin binding was decreased in both obese (P less than 0.01) and non-obese (P less than 0.01) offspring when compared with the respective controls. Scatchard analysis of the binding data and the higher insulin concentrations required to achieve 50% inhibition of tracer binding indicated decreased receptor affinity in both obese and non-obese offspring. Analysis by average affinity profiles also indicated decreased receptor affinity, as shown by a lower average affinity constant Kc for the empty sites, in the offspring in comparison to that of controls (P less than 0.001). Abnormalities in insulin binding to its receptor along with decreased affinity in the face of normal glucose tolerance may be an early biochemical marker of potential diabetes in this group at high risk of developing diabetes.

Adult↗

Erythrocyte insulin binding abnormalities in fibro calculous pancreatic diabetes.

Insulin binding to erythrocyte insulin receptors was studied in 17 patients (13 men and 4 women) with fibrocalculous pancreatic diabetes mellitus (FCPD) and compared with that of 14 newly diagnosed NIDDM patients matched for age, sex and severity of hyperglycemia, and 14 age and sex-matched non-diabetic control subjects. In the uncompensated diabetic state, mean (+/- S.D.) specific binding of insulin was lower in both FCPD and NIDDM patients, compared with non-diabetic controls (P less than 0.001). Control of diabetes with short term therapy (2-6 weeks) resulted in a significant improvement in the mean specific insulin binding in both FCPD and NIDDM patients (P less than 0.001) due to increased binding affinity in the former, and increased affinity and the number of binding sites in the latter. As compared to short term therapy, chronic therapy (5-8 months) in FCPD patients resulted in a marginal decrease in specific insulin binding. However, this was still significantly higher than the basal value (P less than 0.05). FCPD patients had an initial low mean basal plasma IRI and a much lower mean stimulated IRI response as compared to NIDDM and non-diabetic controls.

Adult↗

Tropical pancreatic diabetes in South India: heterogeneity in clinical and biochemical profile.

Clinical and biochemical studies were carried out in 33 patients with diabetes secondary to chronic calcific, non-alcoholic pancreatitis (tropical pancreatic diabetes) and in 35 Type 2 (non-insulin-dependent) diabetic patients and 35 non-diabetic subjects. Despite lower body mass indices, only 25% of patients with tropical pancreatic diabetes had clinical evidence of malnutrition. There was no history of cassava ingestion. Mean serum cholesterol concentration was significantly lower in the tropical pancreatic diabetic patients (p less than 0.01) in comparison with the Type 2 diabetic patients or non-diabetic subjects, due to a significantly decreased concentration of LDL cholesterol (p less than 0.01) and VLDL cholesterol (p less than 0.05). Basal and post-glucose stimulated concentrations of serum C-peptide were highest in those pancreatic diabetic patients (n = 11) who responded to oral hypoglycaemic drugs, intermediate in the majority (n = 17), who were insulin dependent and ketosis resistant and negligible in a small sub-group (n = 5) who were ketosis prone. The occurrence of microangiopathy in pancreatic diabetic patients was common and similar to that in Type 2 diabetic patients. Thus, tropical pancreatic diabetes in South India appears to be heterogeneous with respect to level of nutrition, severity of glucose intolerance, B-cell function, response to therapy and the occurrence of microvascular complications.

C-Peptide↗

Structural and kinetic studies on the activators of succinate dehydrogenase.

1. Diverse classes of compounds such as dicarboxylates, pyrophosphates, quinols and nitrophenols are known to activate mitochondrial succinate dehydrogenase (EC 1.3.99.1). Examples in each class -- malonate, pyrophosphate, ubiquinol and 2,4-dinitrophenol -- are selected for comparative studies on the kinetic constants and structural relationship. 2. The activated forms of the enzyme obtained on preincubating mitochondria with the effectors exhibited Michaelian kinetics and gave double-reciprocal plots which are nearly parallel to that of the basal form. On activation, Km for the substrate also increased along with V. The effectors activated the enzyme at low concentrations and inhibited, in a competitive fashion, at high concentrations. The binding constant for activation was lower than that for inhibition for each effector. 3. These compounds possess ionizable twin oxygens separated by a distance of 5.5 +/- 0.8 A and having fractional charges in the range of -0.26 to -0.74 e. The common twin-oxygen feature of the substrate and the effectors suggested the presence of corresponding counter charges in the binding domain. The competitive nature of effectors with the substrate for inhibition further indicated the close structural resemblance of the activation and catalytic sites.

Dinitrophenols↗

Effect of treatment with alpha-p-chlorophenoxyisobutyrate and of cold exposure on the distribution of lipids in hepatic mitochondria.

Administration of alpha-p-chlorophenoxyisobutyrate (0.25% in the diet) to rats increased the liver weight, hepatic contents of ubiquinone and mitochondrial protein with no effect on the sterols. The increase was progressive with the period of drug treatment and was potentiated by simultaneous cold exposure. Withdrawal of the drug treatment as well as the cold stress resulted in a return of the liver weight and mitochondrial content to normal levels but this was not so for the ubiquinone content. Treatment with alpha-p-chlorophenoxyisobutyrate with or without cold exposure also resulted in a small but significant increase in the mitochondrial lipids which could be accounted for completely by an increase in the phospholipids with no change in the neutral lipid content. Analysis of the individual phospholipids showed that the drug treatment per se resulted in a specific increase in phosphatidylethanolamine content whereas simultaneous cold exposure or cold per se showed an increase in phosphatidylcholine. Cardiolipin content was unaffected. Mitochondria isolated from drug-treated animals maintained at an ambient or low environmental temperature showed a small but significant decrease in the respiratory control index for the oxidation of glutamate and malate whereas the coupled oxidation rates and ADP/O ratios were normal. Such a feature was also observed in the animals exposed to short periods of cold stress without the drug treatment. In all the cases the oxidation of succinate was unaffected. The role of accumulated phospholipids in the mitochondrial membranes in drug treatment and cold exposure is discussed in relation to the possible involvement in increased thermogenesis.

Animals↗

Decreased insulin binding in Asian Indian women with gestational diabetes mellitus.

Insulin binding to erythrocyte insulin receptors was studied in 10 women with gestational diabetes and compared with 10 matched, normal, pregnant women and 10 normal, non-pregnant controls, with no family history of diabetes. Pregnant women had higher mean fasting and post-glucose plasma immunoreactive insulin (IRI) compared to non-pregnant controls (p less than 0.001). Women with gestational diabetes had higher mean fasting and post-glucose plasma glucose levels and a lower mean specific binding of insulin when compared with the other two groups (p less than 0.001). The decreased insulin binding was significant only at lower insulin concentrations (0.2-2 ng/ml) when compared with those of normal pregnant women (p less than 0.01), suggesting decreased receptor affinity with no change in receptor number. In addition, an increased mean ED50 value for 50% inhibition of maximal binding and a lower mean average affinity constant Ke (empty site) obtained in gestational diabetes in comparison to the other two groups also suggested de decreased affinity of the receptor. The finding that pregnancy with normal glucose tolerance was not accompanied by changes in insulin binding against decreased insulin binding and affinity observed in gestational diabetes suggested a pathogenetic role for impaired insulin binding as one of the factors responsible for insulin resistance and hyperglycemia in gestational diabetes.

Administration, Oral↗

Errors in clinical assessment of glycemic control in patients with non-insulin-dependent diabetes mellitus.

Errors in the assessment of glycemic control by clinicians, using the conventional method, based on random blood glucose and clinical parameters other than HbA1, were assessed in 125 non-insulin-dependent diabetic (NIDDM) patients (Group B). The expected mean post-prandial plasma glucose concentrations (y) for these patients were obtained from their HbA1 values (x) using the regression equation y = 39.6 X x - 157.6. This equation was derived using the data from 35 NIDDM patients (Group A), in whom mean post-prandial plasma glucose concentrations (measured twice daily), correlated excellently (r = 0.82; n = 100; p less than 0.001) with mean HbA1 values (measured monthly) determined over a period of 3 months. A comparison of the observed and expected post-prandial plasma glucose concentrations in Group B indicated that only an overall 42% of the total (n = 455) observed values (as against 60% in Group A) fell within the 99% confidence limits of the expected mean value. Fifty-eight % of the observed plasma glucose values fell outside the expected range of which 36% were underestimates and 22% were overestimates. Thus, we concluded that even in patients with stable diabetes the physician's assessment of the overall degree of glycemic control should be based on both plasma glucose and HbA1 concentrations for optimizing therapeutic measures.

Blood Glucose↗

Rapid improvement in insulin binding to erythrocyte insulin receptors in non-insulin-dependent diabetes mellitus during therapy.

Insulin binding to erythrocyte receptors was studied in 36 newly diagnosed male subjects with NIDDM, treated with diet alone (Group I; n = 10) or diet + glibenclamide (Group II; n = 12) or diet + glibenclamide + metformin (Group III; n = 14). Fourteen matched non-diabetic subjects were also studied as controls. Initially, mean (+/- SD) specific insulin binding was lower in NIDDM patients than in controls (p less than 0.001), due to decreased receptor number and affinity. Control of diabetes with short-term therapy (10 +/- 2 days) resulted in significantly increased specific insulin binding in Groups II and III (p less than 0.001). A marginal increase was observed in Group I (p less than 0.01). The improved insulin binding observed in Group II and III patients after short-term therapy was maintained even after long-term therapy (9 +/- 1 months). Analysis of the insulin binding data by Scatchard plots and average affinity profiles indicated increased receptor number and affinity after short-term therapy. However, changes in affinity were reversed with long-term therapy in Groups II and III and the predominant effect appeared to be an increase in the number of binding sites.

Adult↗

Increased LDL cholesterol in non-insulin-dependent diabetics with maculopathy.

Serum cholesterol and its various lipoprotein fractions and triglycerides were measured in 50 non-insulin-dependent diabetic patients, 25 without retinopathy (group A) and 25 with diabetic maculopathy (group B) initially before control of diabetes, and again, after achieving good metabolic control. The lipid parameters were also estimated in 25 healthy non-diabetic subjects. The groups were well matched for sex, age, duration of diabetes and body weight. Mean serum total cholesterol and LDL cholesterol levels were significantly higher in group B when compared to group A, before and after achieving good metabolic control of diabetes (p less than 0.001). Mean total/HDL cholesterol and mean LDL/HDL cholesterol ratios were also significantly increased in group B as compared to group A (p less than 0.01) both before and after good diabetic control in these patients. Mean serum HDL and VLDL cholesterol and triglyceride concentrations were similar in groups A and B. The mean serum lipid concentrations in the diabetic patients without retinopathy (group A) were comparable to those of non-diabetic subjects.

Adult↗