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M S Kappy

Publications and source records attributed to M S Kappy.

At least 37 records · Page 2Linked to original sources
PubMed1986

Insulin is a growth-promoter of the developing brain: possible implications for the infant of the diabetic mother.

The combination of diabetes mellitus and pregnancy was once associated with significantly increased morbidity and mortality for mother and baby. Advances in the obstetric management of the mother with diabetes and parallel advances in the management of the infant of the diabetic mother (IDM) have lowered the morbidity and mortality in many centers to near those for pregnancies in the non-diabetic woman. A significant increase still exists in the prevalence of congenital malformations in IDMs. Recent animal studies have shown that these malformations are related to maternal hyperglycemia early in the pregnancy, and that if it is controlled with insulin during the critical period of embryologic development, then the malformations may be prevented.

Animals↗
PubMed1985

Developing rat brain binds monoiodinated insulin isomers similarly to other extrahepatic target tissues.

We recently reported a series of binding and metabolic studies which led to the conclusion that the developing rat brain is a target tissue for insulin. Since insulin target tissues (extrahepatic) are capable of differentiating between various monoiodoinsulin isomers, we measured the binding of the B26 monoiodoinsulin isomer compared to the A14 in newborn rat brain preparations to determine if the developing rat brain shared the same relative binding of these isomers (viz. B26 greater than A14) with other extrahepatic tissues. The B26 isomer bound 1.57, 1.50 and 1.34 times as much as did the A14 to brain membranes, glia and neurons, respectively, whereas both isomers were bound equally by liver plasma membranes. Competition-inhibition curves were generated using homologous unlabeled (127I) insulin isomers. Binding of the B26 isomer was greater than the A14 at all concentrations. Scatchard plots showed that the receptor concentrations for the two isomers were similar, and affinity profiles showed that the differences in binding could be accounted for by the greater affinity of the receptors for the B26 isomer. The results indicate that the developing rat brain shares with other extrahepatic insulin target tissues a greater affinity for B26 monoiodoinsulin isomer compared to A14. Future studies of insulin binding should avoid using mixtures of iodinated insulins so that a uniform interpretation of data is made possible.

Animals↗
PubMed1985

Insulin stimulates macromolecular synthesis in cultured glial cells from rat brain.

The effect of insulin on macromolecular synthesis in glial cells cultured from brains of 1-day-old rats was studied to investigate the role of insulin in brain growth. Insulin caused a dose-dependent stimulation of protein synthesis (measured by [3H]valine incorporation into protein) that became significant by 7 nM insulin. Maximal stimulation of protein synthesis of 145% of control occurred with 18 nM insulin. Long-term protein synthesis was also stimulated to 136% of control by insulin in a dose-dependent manner after 6 days of insulin incubation. Insulin also stimulated net RNA and DNA synthesis (measured by [3H]uridine and [3H]thymidine incorporation into RNA or DNA, respectively) with significant stimulation by 2 nM insulin. Net RNA synthesis stimulation was maximal at 120% of control by 18 nM insulin. Plateau stimulation of DNA synthesis of 175% of control was reached by 200 nM insulin. The effects of insulin on glial protein and RNA synthesis appear to be mediated completely by the insulin receptor. Insulin, in physiological concentrations, stimulated glial DNA synthesis via its interaction with the insulin receptor (46% of total response). At supraphysiological concentrations insulin may have stimulated DNA synthesis via its cross-reactivity with the insulinlike growth factor I receptor (54% of total response). Thus insulin, at concentrations known to exist in the brain, stimulates the processes necessary for growth in the glial cell and is an important growth factor in the developing rat brain.

Animals↗
PubMed1984

Insulin binds to specific receptors and stimulates 2-deoxy-D-glucose uptake in cultured glial cells from rat brain.

The kinetics of 125I-insulin binding and physiological activity of insulin on glial cells cultured from brains of 1-day-old rats have been studied. Binding of 125I-insulin to cultured glial cells was specific, reversible, and time-dependent. Porcine and chicken insulin competed equally for 125I-insulin binding while other hormones or insulin analogs competed in proportion to their insulin-like biological activity. Incubation of glial cultures with insulin resulted in a time- and dose-dependent stimulation of 2-deoxy-D-glucose uptake. Maximal stimulation (190% of control) was observed with 18 nM insulin, and 0.1 nM insulin caused half-maximum effect. The stimulatory effect of insulin on 2-deoxy-D-glucose uptake was due to its effect on Vmax without affecting the Km. These observations suggest that insulin stimulates glucose uptake in glial cells cultured from rat brain, the effect mediated by insulin specific receptors.

Animals↗
PubMed1984

Insulin inhibits pyramidal neurons in hippocampal slices.

Recent studies have confirmed the presence of insulin receptors in the rat brain although their function has still not been well defined. The present study explores the possibility that insulin receptors in the brain can alter or contribute to central neurotransmission. Insulin caused a dose-dependent inhibition of hippocampal pyramidal neurons. The pattern of inhibition mirrored the binding kinetics of insulin in the hippocampus. Two related peptides, proinsulin and desoctapeptide insulin, had neuronal effects consistent with their binding to insulin receptors in the brain. Proinsulin was effective in doses 30-fold greater than insulin, whereas desoctapeptide insulin had little or no effect. These observations indicate that the inhibitory effect of insulin in this tissue may be insulin receptor-mediated and support a previously suggested functional role of insulin in the central nervous system.

Animals↗
PubMed1984

The longest illness. Effects of nuclear war in children.

The destruction of civilization that would follow a nuclear war would render any disaster ever recorded insignificant. Millions of people would perish during the first few hours, and many more would die in the months to come. Survival would exist only in the strictest sense of the word, since societal disorganization, famine, drought, darkness, and nuclear winter would envelope the earth. The comparative frailty of children and their dependence on adults would render them most susceptible to the acute effects of a nuclear holocaust. Furthermore, studies of the Hiroshima and Nagasaki, Japan bombings showed a disproportionate propensity for children to experience leukemias and other cancers years after the bombings. There were also great increases in perinatal deaths and cases of microcephaly and retardation in children exposed in utero to the bombs. In the event that there are future generations after a nuclear war, the issue of heritable genetic effects will become important. Suggestions of permanent genetic damage are emerging from the Hiroshima and Nagasaki studies. By comparison, the genetic effects of modern weaponry will be incalculable.

Blast Injuries↗
PubMed1983

Insulin binding to monocytes in obese patients treated with carbohydrate restriction and changes in physical activity.

Mean [125I]insulin binding to circulating monocytes was low (P less than 0.05 compared to normal controls) in nine obese patients on a weight-maintaining diet in which 45% of the calories were carbohydrate. On a 10% carbohydrate diet, insulin binding was normal in six of seven obese patients. Plasma insulin concentrations were elevated in obese patients on both diets. No correlation was found between insulin binding and plasma insulin concentration. Glucose intolerance and hyperinsulinemia were worsened by keeping the patients at rest and were improved by having the patients walk 3-4 miles/day. The change in physical activity had no effect on [125I]insulin binding to monocytes. We conclude that 1) insulin binding to monocytes in obese patients is generally low in patients on a carbohydrate-rich diet, but is normal in patients on carbohydrate-restricted diets; 2) down-regulation of insulin receptors does not necessarily occur in the presence of hyperinsulinemia: and 3) a walking program results in an improvement in glucose tolerance and hyperinsulinemia that is not associated with a change in insulin binding.

Adult↗
PubMed1983

Insulin binding is a specific marker of fetal erythrocytes in ruminants.

The ability of erythrocytes (RBC) from sheep and cattle of various gestational and postnatal ages to bind insulin specifically was studied. Insulin binding to RBC decreased as gestational and postnatal age advanced and was absent in blood obtained from adult animals. Maximal percentage 125I-insulin bound to RBC (3.6 X 10(9)/ml) was highest in the fetuses of sheep and cattle (7.3 +/- .6 and 7.8 +/- .9, respectively) compared to postnatal animals (2.3 +/- .2 and 2.2 +/- .3, respectively), or adults (no binding) of the same species. The decrease in binding began antenatally, and binding was projected to be insignificant by the end of the second postnatal month. Most of the observed decrease was due to a progressive decrease in the number of receptors on the cell surface. The time course of this phenomenon, as well as the total absence of insulin receptors on the RBC of adult ruminants, provides independent evidence that two distinct populations of RBC in ruminants exist. The gradual appearance of the adult RBC with no insulin binding results in a decrease in observed binding to RBC in a given blood specimen as fetuses and postnatal animals age.

Animals↗
PubMed1982

Adult-level insulin binding is present in term fetal rat CNS membranes.

Insulin binding was measured using partially-purified membranes prepared from the brains of term fetal and adult rats as the source of receptors. The membranes from the fetal rat brains bound at least as much insulin as did those from the adult rats at all concentrations of insulin used. This finding supports our hypothesis that insulin contributes to the postnatal growth of the rat brain.

Animals↗
PubMed1981

Ontogeny of erythrocyte insulin binding in the sheep.

The ontogeny of insulin binding in the sheep was studied using the erythrocytes (RBCs) of 31 fetuses, 10 lambs, and 5 adult animals. Six fetuses were studied on three occasions over a 2-week period from 120--135 days of gestation to provide longitudinal data on changes in insulin binding. Maximal percent binding of [125I]iodoinsulin and receptor concentration decreased significantly as the age of the animal increased (r = 0.76, P less than 0.001 and r = --0.49, P less than 0.001, respectively). Total loss of insulin binding to RBCs was estimated to occur in the second postnatal month, and the RBCs from the adult sheep showed no specific insulin binding. The osmotic fragility of RBCs in each developmental group of animals was also studied to assess possible differences in RBC membrane properties. RBC osmotic fragility was significantly lower in fetuses than in adult sheep (osmotic fragility 50 = 0.55% phosphate-buffered saline vs. 0.76% phosphate-buffered saline, respectively; P less than 0.001). The data suggest that fetal RBCs of lower osmotic fragility and high insulin binding capacity are progressively replaced during late prenatal and early postnatal life by adult-type RBCs of increased osmotic fragility and lacking binding capacity for insulin. The timing of the disappearance of insulin binding to RBCs coincides with the final transition in the animals from a monogastric to a ruminant metabolic state, and may reflect a change in the need for insulin with age.

Aging↗
PubMed1980

Erythrocyte insulin binding in obese children and adolescents.

Insulin binding studies in obese patients have been limited to adults due to the relative inaccessibility to tissues for study in the pediatric age group. Insulin binding to the erythrocytes (RBCs) of 9 obese pre-pubertal children, 8 obese adolescents, and 10 obese adults was studied. There was a mean decrease of 15% of insulin binding in the obese patients (P < 0.02 vs. controls). Calculation of receptor concentrations by means of Scatchard plots showed a mean 30% reduction in insulin receptors on the RBCs of obese patients as a group (P < 0.001 vs. controls). The binding of insulin and receptor concentration were inversely proportional to the fasting plasma insulin concentration (= -0.60 and -0.44, respectively). These correlations were significant (P < 0.001 and P < 0.05, respectively). The mean empty site receptor affinity (Ke) was significantly increased in obese patients, but only partially compensated for the loss of receptors with respect to total insulin bound over the physiological range of insulin concentrations. The results of binding studies in the obese adults were similar to those in the children and adolescents, and agreed with published reports of insulin binding in obese adults using adipocytes or monocytes as the source of insulin receptors. The observed decrease in insulin binding to the RBCs of obese children and adolescents correlated with fasting hyperinsulinemia and, therefore, may contribute to the etiology of the insulin resistance or glucose intolerance observed in these patients.

Adolescent↗
PubMed1980

Erythrocyte insulin binding in insulin-dependent diabetes mellitus: lack of relationship to duration and control of diabetes in children and adolescents.

Insulin binding was measured in the erythrocytes (RBCs) of four children and 12 adolescents with insulin-dependent diabetes mellitus in the basal (fasting, nonketotic) state. Children and adolescents with insulin-dependent diabetes mellitus showed normal binding of insulin to their RBCs when expressed as the total insulin bound over the physiologic range of insulin concentrations. The insulin receptor concentration and receptor binding affinity for insulin were also normal. These parameters of insulin binding were not correlated with either the duration of diabetes or the degree of diabetic control in the patients. Since insulin binding by erythrocytes has been shown to reflect binding by traditional target tissues (liver, fat), the data suggest that alterations in binding of insulin to cells in children and adolescents with insulin-dependent diabetes mellitus probably play little, if any, role in the response of these patients to exogenous insulin or in the control of their glucose metabolism in the basal state.

Adolescent↗
PubMed1979

Low-dose intravenous insulin in the treatment of diabetic ketoacidosis.

Continuous slow intravenous infusion of insulin was used in 52 episodes of diabetic ketoacidosis. No complications of therapy, ie, hypoglycemia, induced hypokalemia, insulin resistance, or cerebral edema, were encountered. Potassium phosphate was given to 47 of the 52 patients. Sodium bicarbonate was administered to only one patient. The hyperglycemia frequently resolved more rapidly than the systemic acidosis; this was managed by adding glucose to the intravenous fluids when the blood sugar concentration decreased to approximately 250 mg/dL; insulin infusion, however, was continued until the acidosis was corrected (venous standard bicarbonate greater than 14 mEq/L). We have found this method of treatment to be safe and simple to administer, and we believe it is the preferred treatment of patients with diabetic ketoacidosis.

Adolescent↗
PubMed1979

Studies of insulin binding in children using human erythrocytes in small amounts of blood.

We have demonstrated specific insulin binding by the erythrocytes (RBCs) of children. Complete binding studies were done using as little as 5 ml of blood. The receptors exhibited competition-inhibition curves and nonlinear Scatchard plots similar to those reported for insulin target tissues, such as the hepatocyte and the adipocyte. Compared with those from adults, the RBCs from children had significantly greater numbers of insulin receptors per cell (P less than 0.05). The total insulin bound by the RBCs from both children and adults, however, was not different over the physiologic range of insulin concentrations. Cord blood RBCs showed greater numbers of receptors per cell than did those from either children or adults; however, the affinity for insulin was similar in both groups. The total amount of insulin bound by cord blood was significantly greater than that in either children (P less than 0.01) or adults (P less than 0.05) over the physiologic range of insulin concentrations. The method used to measure insulin binding by erythrocytes and relatively little intra- and interassay variability, and there was little diurnal variation in binding. Storage of heparinized blood at 4 degree C for 24--36 h had no effect on insulin binding by the RBCs. We conclude that the measurement of insulin binding by RBCs from small volumes of blood may be particularly useful in the study of infants and children with disorders of carbohydrate metabolism to elucidate the role, if any, of abnormal receptor function in their condition.

Adolescent↗