Critical Factors in Excessive Serum-Insulin Response to Glucose Obesity in Maturity-Onset Diabetes and Growth Hormone in Acromegaly

Karam, John H.; Pavlatos, FotiosCh.; Grodsky, GeroldM.; Forsham, P. H.

doi:10.1016/s0140-6736(65)91026-3

Cited by 129 publications

(21 citation statements)

References 9 publications

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“…In these patients it seems reasonable to suggest that hyperglycemia is secondary to insulin resistance, and the exaggerated insulin response can be viewed as a compensatory mechanism aimed at minimizing glucose intolerance. On the other hand, this explanation cannot be used to account for the hyperglycemia in the adult onset diabetic subjects presented in this report, since diabetic patients with fasting hyperglycemia have insulin responses to glucose which are less than normal (14,15). Therefore, it would appear that the hyperglycemia in these patients could result from both decreased insulin secretion and increased insulin resistance, and it is not immediately apparent which of the two is most important.…”

Section: Discussionmentioning

confidence: 67%

Demonstration of insulin resistance in untreated adult onset diabetic subjects with fasting hyperglycemia.

Ginsberg¹,

Kimmerling²,

Olefsky³

et al. 1975

J. Clin. Invest.

217

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A B S T R A C T We have used a continuous intravenous infusion of glucose (6 mg/kg/min), insulin (80 mU/ min), epinephrine (6 Ag/min), and propranolol (0.08 mg/min) to directly assess insulin resistance in 14 untreated adult onset diabetics with a mean (±SE) fasting plasma glucose level of 217±17 mg/100 ml. During the infusion endogenous insulin secretion is inhibited and steady-state plasma glucose and insulin levels are achieved after 90 min. Since similar steadystate levels of plasma insulin are achieved in all subjects, the plasma glucose concentration observed during the steady-state period is a measure of an individual's insulin resistance. Under these conditions, the mean (±SE) steady-state plasma glucose level of the 14 diabetic patients was 350±16 mg/100 ml, while that of 12 normal subjects was 121±4 mg/100 ml. Additional studies were performed in which control subjects and patients with diabetes had their fasting plasma glucose levels acutely raised or lowered to comparable levels before receiving the basic infusion mixture of glucose, insulin, epinephrine, and propranolol. The results of these studies indicated that differences in initial plasma glucose levels could not account for the different glucose responses of the two groups to the basic infusion.Finally, the mean (±SE) steady-state plasma glucose level of 104±17 mg/100 ml observed during the same basic infusion in five patients with fasting hyper-

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Section: Discussionmentioning

confidence: 67%

Demonstration of insulin resistance in untreated adult onset diabetic subjects with fasting hyperglycemia.

Ginsberg¹,

Kimmerling²,

Olefsky³

et al. 1975

J. Clin. Invest.

217

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“…The magnitude of the rebound after epinephrine was variable but appeared to be greater in those subjects with larger IRI responses to glucose, glucagon, or tolbutamide alone. The variation in individual response was not related to obesity (11) since none of the patients was obese, nor was it found to correlate well with sex, body surface area, height, or weight. No measurements of plasma epinephrine levels were made, and it is possible these might have correlated better with the degree of epinephrine inhibition.…”

Section: Discussionmentioning

confidence: 81%

The effect of epinephrine on immunoreactive insulin levels in man.

Porte¹,

Graber²,

Kuzuya³

et al. 1966

J. Clin. Invest.

506

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The mechanisms by which epinephrine elevates the blood sugar have been of considerable interest for more than 25 years. In an extensive review in 1956, Ellis suggested that the two major influences on glucose metabolism were increased glycogenolysis in the liver and peripheral tissues, and direct inhibition of glucose uptake by muscle (1). There is, however, the additional possibility that epinephrine might decrease insulin levels. The introduction of insulin immunoassay (2, 3) has allowed us to examine this third hypothesis in man. Our data show that epinephrine infusion is not associated with a rise in serum immunoreactive insulin (IRI) despite significant hyperglycemia. In addition, epinephrine was found to inhibit the expected rise in IRI after administration of exogenous glucose, glucagon, and tolbutamide. medical illness. None had any close relative who was known to be diabetic. All were within 15% of their ideal body weight.' Approximately 20% had been previously tested at random with the 100-g oral glucose tolerance test and were normal by the criteria of Mosenthal and Barry (4). All had fasting plasma glucose less than 105 mg per 100 ml. For the study, no solid food was taken after the previous evening meal at 6 to 7 p.m., and no liquids except water were taken after midnight. MethodsNo smoking was allowed on the day of the test. Upon arriving at the Clinical Research Center for study the volunteer was put to bed, and a slow intravenous 0.85%oNaCl drip was begun through each of two indwelling venous plastic catheters. Blood samples were taken through one catheter, and drugs or glucose was infused through the other with a constant drive syringe infusion pump. No anticoagulants were given to the patient or were present in the sampling syringe. Blood samples were obtained every 15 minutes and sampled for measurements of glucose, IRI, free fatty acids (FFA), and glycerol. Blood for insulin assay was allowed to clot for I hour at room temperature, and the serum was frozen at -190 C until analyzed by the double antibody immunoprecipitation technique (5). Neither epinephrine (1 ,ug per ml) nor tolbutamide (50 mg per ml) had any measurable effects when added to the immunoassay system in vitro. The glucagon preparation assayed 5 to 7 AsU of immunoreactive insulin per microgram of glucagon. This amount of insulin was considered to have no significant effect upon serum IRI with the infusion rate of glucagon used (5 sAg per minute). The human insulin standard was supplied.2 Blood samples for FFA, glucose, and glycerol were anticoagulated with heparin and kept chilled at 40 C. The plasma was separated by centrifugation in the cold and frozen at -19°C for future analysis. FFA were titrated against standard base by a modified Dole procedure (6). Plasma glucose was measured by a Technicon autoanalyzer with a ferricyanide reagent. Glycerol was measured by the enzymatic method of Wieland (7) with commercially available glycerokinase and glycerophosphate dehydrogenase.8

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“…It should, however, be noted that the plasma growth hormone concentrations reported by Fraccaro et al (1960) are based on the tibia line assay and the results given by this technique are some 1000 times higher than those given by current radio-immuno assays. An excessive serum insulin response after glucose has been reported in acromegaly (Grodsky & Forsham, 1960;Yalow & Berson, 1960) and this has been further investigated by Karam, Grodsky, Pavlatos & Forsham (1965). An analysis of their results shows that some of their acromegalics had elevated plasma insulin levels, but normal sensitivity in the standard insulin tolerance test.…”

Section: Discussionmentioning

confidence: 98%

Carbohydrate Metabolism and Pituitary Function in Gonadal Dysgenesis (Turner's Syndrome)

Jackson¹,

Buchanan²,

McKiddie³

et al. 1966

Journal of Endocrinology

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An oral glucose tolerance test was performed in eight patients with gonadal dysgenesis and in two a diabetic response was found. The plasma insulin levels were estimated in response to the glucose load and were abnormal in five out of the six patients examined.The blood sugar response to the standard insulin tolerance test was normal in six patients and showed increased insulin sensitivity in two. Plasma cortisol concentration was measured in response to the hypoglycaemia induced by insulin and in seven out of the eight patients rose considerably indicating a normally functioning pituitary-adrenal system.

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Critical Factors in Excessive Serum-Insulin Response to Glucose Obesity in Maturity-Onset Diabetes and Growth Hormone in Acromegaly

Cited by 129 publications

References 9 publications

Demonstration of insulin resistance in untreated adult onset diabetic subjects with fasting hyperglycemia.

Demonstration of insulin resistance in untreated adult onset diabetic subjects with fasting hyperglycemia.

The effect of epinephrine on immunoreactive insulin levels in man.

Carbohydrate Metabolism and Pituitary Function in Gonadal Dysgenesis (Turner's Syndrome)

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