Albert Castro

Plasma Insulin and Glucose Responses of Healthy Subjects to Varying Glucose Loads During Three-hour Oral Glucose Tolerance Tests

The plasma glucose and plasma immunoreactive insulin concentrations of twelve healthy, nonobese, adult subjects were compared following administration of oral glucose loads of 50, 75 and 100 gm., and 1.75 gm./kg. body weight. The time of occurrence and the magnitude of maximal plasma glucose and insulin concentrations were unaffected by the 25 gm. increases in glucose load. The 50 gm. glucose load gave the smallest plasma glucose response during the three-hour tests and this response was statistically distinguishable from the plasma glucose responses due to the 100 gm. and 1.75 gm./kg. loads (p < 0.05). The plasma glucose responses due to the other loads did not differ from each other. Insulin responses, estimated by either summing allthe plasma insulin values or by measuring the areas under the curves, increased approximately 35 per cent with the first 25 gm. glucose load increment (50 to 75 gm.) and 27 per cent with the second 25 gm. load increment (75 to 100 gm.) during the three-hour study. The differences in insulinresponses between the 50 gm. load and the 100 gm. or 1.75 gm./kg. loads were highly significant (p < 0.01) while the difference between the insulin responses following the 75 gm. and 1.75 gm./kg. loads had lower significance (p < 0.05). Differences in insulin responses of the other loads were not significant. Increases in glucose loads above 120 gm. did not further increase the insulin response. This provides evidence that maximal insulin responses provoked by an oral glycemic stimulus alone in subjects are achieved with 100 gm. A wide range was observed in the plasma insulin concentrations among these healthy individuals for any given load, at any one time, and was probably due to biological variation. The fact that incremental changes in glucose load particularly influenced plasma glucose and insulin concentrations relatively late in the glucose tolerance tests, and that mean insulin peakconcentrations did not differ, indicates that increasing glucose load results in a more prolongedinsulinogenic stimulus rather than the acute release of greater quantities of insulin relatively abruptly. These studies provide evidence that the response associated with increasing glucose load is to some extent a function of the quantity of glucose ingested, and that the significant increases in insulin response commonly occur in association with concurrent alterations in plasma glucose concentrations. The results also indicate that the 50 gm. glucose load results in a different plasma glucose response than does the 100 gm. and 1.75 gm./kg. loads and consequently requires different criteria for interpretation of glucose tolerance testing.

Decreased Rat Hepatic Guanylate Cyclase Activity in Streptozotocin-induced Diabetes Mellitus

Guanylate cyclase is found in virtually all cells, but its physiologic role and the effect of hormones on its activity have not been clarified. Hepatic soluble guanylate cyclase activity (37,000 g supernatant) in rats with diabetes-mellitus-like syndrome induced by streptozotocin, 65 mg./kg. i.V., was 140 ± 8 pmoles accumulated/mg. protein/10 min. (n = 13 rats) as against 279 ± 16 pmoles accumulated/mg. protein/10 min. (n = 12 rats) in normal rats. The average blood sugar for the 12 normal rats was 100 ± 4 mg./100 ml. and 546 ± 32 mg./100 ml. for 13 diabetic rats. The decreased soluble hepatic guanylate cyclase activity in diabetic rats was completely restored to normal with 10 U. regular insulin, i.p. The maximum increase in guanylate cyclase activity was observed as early as five minutes and as late as two hours after insulin administration. Insulin restoration of guanylate cyclase was dose-related over a range of 1 U. to 10 U., i.p. Hepatic cyclic GMP levels in vivo paralleled in-vitro guanylate cyclase activity, being 29 ± 0.4 pmoles/gm. wet weight in normals, 17 ± 0.4 pmoles/gm. wet weight in streptozotocin-diabetic rats, and 38 ± 0.4 pmoles/gm. wet weight two hours after the injection of 10 U. regular insulin. We conclude that rat hepatic guanylate cyclase is decreased in streptozotocin-induced diabetes and that insulin modulates this enzyme. The administration of exogenous insulin in normal animals did not further augment hepatic guanylate cyclase activity.

INSULIN PRODUCTION AND GLUCOSE TOLERANCE IN PATIENTS WITH GRANULOMA ANNULARE

Summary.— Ten patients with granuloma annulare were studied for evidence of carbohydrate intolerance. By traditional criteria, 2 had an abnormal glucose tolerance test. Of the remaining 8,3 had an abnormal cortisone‐glucose tolerance test. The findings indicate a higher incidence (50%) of glucose intolerance in these patients than is found in the average population. In the cortisone‐glucose tolerance test, plasma insulin response to glucose loading was significantly lower in the population of 10 patients with granuloma annulare than in a normal control group. The remaining 4 granuloma annulare patients with normal glucose values in both the standard and cortisone‐induced glucose tolerance tests were aiso evaluated by measuring plasma insulin response to glucose loading. These 4 patients, when evaluated as a group, demonstrated also a significantly lower insulin response to glucose than the control population. These results suggest a decreased pancreatic beta cell sensitivity to glucose stimulation in patients with granuloma annulare.

Glucose, insulin, HGH, and cortisol plasma levels in granuloma annulare patients during glucose tolerance and cortisone glucose tolerance test

Glucose, insulin, human growth hormone and cortisol levels are reported during both a standard glucose tolerance test and a cortisone-glucose tolerance test in eleven Granuloma Annulare patients and five healthy subjects. Although little difference seemed to exist between these two groups during the standard GTT they differed significantly (p

A radioimmunoassay for deoxycorticosterone in human peripheral plasma using sephadex LH-20 chromatography.

Se reporta un nuevo método para medir desoxicorticosterona en plasma, usando cromatografía de columna LH-20 y radioinmunoensayo. Las cantidades de plasma necesarios para dicho ensayo son mínimas (2 ml) comparadas con otros métodos en la literatura, es un método practico, sensillo y rápido. Resultados así obtenidos han sido comparados con otros métodos, dichos resultados son más precisos y sensitivos para medir valores de desoxicorticosterona en plasma humano.

Effect of diazoxide in plasma glucose and insulin concentrations after acute glycemic stimulation and intravenous tolbutamide

Abstract Five healthy young subjects were subjected to glucose tolerance and tolbutamide tests before and after diazoxide administration. The glucose tolerance tests were made after two challenges with 100 g of glucose. A 5-day treatment with diazoxide (100 mg t.i.d.) lowered the plasma insulin response consistently throughout the second glucose challenge, but did not lower the plasma insulin in response to the tolbutamide challenge. Since tolbutamide stimulates a normal insulin release after diazoxide administration, it appears that the diazoxide did not impair the synthesis and storage of insulin, but that diazoxide interferes with the release of insulin during the glucose challenge. While diazoxide caused a decreased plasma insulin concentration during the glucose challenge, the plasma glucose concentration was not increased in four of the five subjects. The results with normal subjects are in contrast with our observations on an insulinoma patient in whom insulin release was enhanced by diazoxide treatment.

The insulin/glucose ratio in children with islet cell tumors of the pancreas

1. The diagnosis of an islet cell adenoma is difficult in children as hyperinsulinism may exist without hyperinsulinemia. 2. Data are presented from three cases and compared with values from ten other cases less than 12 years old. 3. These figures suggest that the best discriminant of hyperinsulinism in childhood may be an elevated plasma insulin/glucose ratio during hypoglycemia.

A new microcolumn for steroid separation in radioimmunoassay.

1. A new type of glass column is herein described for separation of steroid molecules. Recovery percentage is increased in two different radioimmunoassays (progesterone, testosterone) when this type of column is compared to others.

Insulin values of normal pancreatic and pancreatic adenomas tissue extracts in children

Abstract Tissues of four pancreatic adenomas of children with clinical hyper-insulinemia and relative hyperinsulinemia, and normal pancreatic tissue were studied. Tissues were extracted and immunoreactive insulin levels measured per gram of dry tissue. Comparisons of findings in two newborn babies with inverted rate glucose/insulin and two children of 11 and 14 yr of age with hyper-insulinemia are reported. Results indicate relative comparable insulin values in adenoma pancreatic tissue in both age groups per gram of tissue, although larger amounts of circulating immunoreactive insulin were found in older children with true hyperinsulinemia. High insulin concentrations were found in one case. These high levels may be related to the severity or type of cell adenoma.

The effect of diazoxide in children with islet cell adenomas.

1. Three children diagnosed preoperatively as having islet cell adenoma of the pancreas were studied. Only one of them exhibited hyperinsulinism during a provocative test. In the remaining two patients the diagnosis was made on the basis of an inappropriately high insulin/glucose ratio during hypoglycemia (relative hyperinsulinemia). The patients responded differently to Diaz-oxide treatment although circulating Diazoxide levels were found to be the same as those of five normal control subjects given similar amounts of the drug. One patient showed an improvement in glucose levels while in another patient the drug was ineffective. The third patient exhibited increased insulin response to a glucose stimulus. All three patients had a partial pancreatectomy with removal of their tumors. The insulin levels in both the tumors and the normal pancreatic tissue are reported.