Plasma Immunoreactive Insulin Concentrations Research Articles

Effects of leucine and isoleucine infused intrapancreatically on glucagon and insulin secretion.

Either leucine or isoleucine dissolved at a concentration of 8 mmoles/kg/1 was administered into the cranial pancreaticoduodenal artery at a rate of 5/6 ml/min to observe any direct effect of these essential L—amino acids on secretion of glucagon and insulin in anesthetized dogs. The infusion of leucine induced a prompt, short—lived, small but statistically significant elevation in plasma immunoreactive glucagon (IRG) concentration and a more than 2–fold augmentation in plasma immunoreactive insulin (IRI) level in the cranial pancreaticoduodenal vein. Plasma IRI concentration in the femoral artery reflected a significant enhancement, but the peripheral plasma level of IRG failed to show any definite rise, signifying a possibility of only a trivial increase in glucagon secretion. An equimolar load of isoleucine did not cause any consistent elevation in the pancreatic vein plasma level of IRG, but raised pancreatic effluent plasma concentration of IRI to about 3–fold values. A significant rise in plasma IRI...

Effect of low-dose human growth hormone on carbohydrate metabolism in children with hypopituitarism

Carbohydrate metabolism was studied in nine growth hormone-deficient children before and one year after treatment with human growth hormone (HGH). Before treatment the mean plasma immunoreactive insulin concentrations following administration of glucose and tolbutamide were significantly reduced. After one year of HGH therapy the mean plasma immunoreactive insulin levels in response to glucose and tolbutamide were greater than before treatment. The pattern of response of plasma free fatty acids, which was abnormal before treatment, returned to normal with therapy. The improvement in insulin responsiveness following HGH suggests that in the absence of growth hormone pancreatic beta cells have a decreased capacity to release insulin which improves following therapy. The effect of HGH on growth may be due, in part, to its insulinogenic activity.

Studies of diabetic instability. II. Tests of insulinogenic reserve with infusions of arginine, glucagon, epinephrine, and saline

Insulinogenic reserve was tested with arginine, glucagon, and epinephrine in eight unstable and four stable diabetics and in five normal subjects. All subjects were fasted and resting during the tests. Blood glucose regulatory stability was measured during near-normal (ambulatory-fed) conditions in the same subjects. Evaluation of insulinogenic reserve was based on changes in plasma immunoreactive insulin (IRI) concentration. The validity of assessing changes in IRI concentration in the presence of insulin-binding antibodies was supported with simultaneous measurements of indirect indications of the biologic effects of insulin. The changes, from base-line values, in IRI concentrations were consistent with and appropriate for the changes in blood glucose and serum free fatty acid and ketone body concentrations. No significant blood glucose fluctuations occurred under unstimulated fasting-resting conditions in any subject (saline test), in contrast to the distinct differences between groups in the amplitude of glycemic excursions during ambulatory-fed conditions. Blood glucose and ketone body concentrations increased steadily during the saline test in unstable diabetics in contrast to stable diabetics and normals. A correlation was evident between insulin secretory ability under resting-fasting conditions and blood glucose regulatory stability during ambulatory-fed conditions. Unstable diabetics had no demonstrable insulinogenic reserve, except for one maturity-onset diabetic with biochemical and clinical characteristics of unstable diabetes. Stable diabetics had demonstrable insulinogenic reserve but less than that of normals.

Human maternal and fetal insulin response to arginine.

Abstract Maternal and fetal insulin response to arginine was examined by infusion of arginine to pregnant women during delivery of their fetuses or to newborn infants directly. Nonpregnant adult subjects were studied as controls. A positive correlation between plasma immunoreactive insulin concentration and plasma arginine concentration was found in the control subjects. The pregnant women at 13 to 18 weeks' gestation had an attenuated insulin response to arginine, whereas the responses of the women during labor and delivery at term were more variable. The fetuses in utero had no significant plasma insulin rise to maternal infused arginine. The newborn infant, however, had attenuated though significant insulin response to intravenous arginine infusion.

Hormonal control of intermediary metabolism in obese hyperglycemic mice. II. Levels of plasma free fatty acid and immunoreactive insulin and liver glycogen.

In mice with genetic obesity, the plasma concentration of total free fatty acid (FFA) was not significantly raised, and no abnormality was detected in the response of the plasma level of FFA to noradrenaline. The plasma concentration of immunoreactive insulin (IRI) in the fed state was higher in obese than lean mice, even if glucose was given to lean mice. The content of liver glycogen was consistently higher in obese mice. Following deprivation of food, plasma concentration of IRI decreased in obese mice, and that of FFA rose at the same rate as in lean mice. In obese mice which had been fasted for twenty-four hours or fed on a restricted quantity of food, the plasma level of IRI remained higher than in lean mice. On oral administration of glucose to fasted mice, the decline in plasma FFA concentration, compared to that in animals which received saline, was similar in obese and lean mice. In response to glucose, the plasma IRI concentration increased rapidly in obese mice. These results suggest that there is no primary impairment of adipose tissue triglyceride breakdown (“lipolysis”) in genetically obese mice, and that the hypersecretion of insulin in response to ingestion of food may more closely reflect their primary disorder.

Submaxillary gland removal. Effects on glucose and insulin homeostasis.

The significance of enlarged salivary glands in diabetes is not clear. The present study was concerned with the possible relationship of the submaxillary glands to glucose tolerance. No significant difference in blood glucose concentrations at any time interval following intravenous glucose administration was observed after removal of the submaxillary glands. Similarly, plasma immunoreactive insulin (IRI) concentrations following intravenous glucose administration were not significantly altered after submaxillary gland removal. Thus, it appears that the normal submaxillary glands do not play a significant role in glucose and insulin homeostasis in the dog.

Stimulation of glucagon secretion by arginine and histidine infused intrapancreatically.

Either arginine or histidine dissolved at a concentration of 8 mmoles/kg/1 was administered into the cranial pancreaticoduodenal artery at a rate of 5/6 ml/min to observe any direct effect of these essential l-amino acids on secretion of glucagon and insulin in anesthetized dogs. The infusion of arginine induced a prompt, short-lived and more than 3-fold elevation in plasma immunoreactive glucagon (IRG) concentration and about 6-fold augmentation in plasma immunoreactive insulin (IRI) level in the cranial pancreaticoduodenal vein. Plasma IRI concentration in the femoral artery reflected a delayed significant enhancement, but the peripheral plasma level of IRG failed to show any definite reflection. An equimolar load of histidine also caused an immediate, significant but much smaller elevation in pancreatic effluent plasma levels of both IRG and IRI. No definite rise in plasma IRG and IRI was elicited in the femoral artery upon local infusion of histidine. Blood sugar concentration was significantly raised...

Study of the relationship between plasma insulin concentration and efficiency of glucose uptake in normal and mildly diabetic subjects.

Removal of glucose-U-C-14 from plasma was studied in normal subjects and in patients with maturity-onset diabetes mellitus. All measurements were made after an overnight fast, during a period in which plasma glucose and immunoreactive insulin concentrations were not changing. The mean irreversible loss rate (ILR) of glucose from the plasma of normal subjects was not different from that of patients with diabetes: mean ILR (± the coefficient of variation) of all patients was 1.36 (± 14 per cent) mg. glucose/kg, body weight per min. This narrow range attests to the similarity of ILR in the patients studied. There was no correlation between glucose ILR and plasma glucose concentration, plasma immunoreactive insulin concentration, or ponderal index. In contrast, fractional glucose irreversible loss rate varied considerably from patient to patient, with a coefficient of variation of 35 per cent. Furthermore, there was a strong negative correlation between plasma glucose concentration and fractional glucose irreversible loss rate (r = −0.82, p < .01). This decrease in efficiency of glucose removal from plasma of hyperglycemic patients was not related to an absolute lack of insulin. It is concluded that net glucose utilization in the fasting state is similar in normal and mildly diabetic patients, and that fasting hyperglycemia is due to a decrease in efficiency of glucose removal which cannot be attributed to absolute insulin deficiency.

Ethnic variability in glucose tolerance and insulin secretion

In an attempt to assess the ethnic variability of diabetes mellitus, a comparative study of the clinical and metabolic features of diabetes in the Navajo Indian and Pennsylvania Amish was undertaken. The Navajo have a mild form of diabetes in which the juvenile ketotic form is unknown and complications are rare, while the Amish have both juvenile and maturity-onset forms with all of the acute and chronic complications. The mean peak plasma immunoreactive insulin (IRI) concentrations attained following oral ingestion of 100 gm of glucose differed significantly in the two groups of diabetics, suggesting that they may represent distinct disorders. There was more than a threefold difference in the maximal plasma IRI response between the normal Navajo and normal Amish, indicating that there is marked ethnic variability in the normal insulin response to an orally given glucose load.

Ethnic Variability in Glucose Tolerance and Insulin Secretion

In an attempt to assess the ethnic variability of diabetes mellitus, a comparative study of the clinical and metabolic features of diabetes in the Navajo Indian and Pennsylvania Amish was undertaken. The Navajo have a mild form of diabetes in which the juvenile ketotic form is unknown and complications are rare, while the Amish have both juvenile and maturity-onset forms with all of the acute and chronic complications. The mean peak plasma immunoreactive insulin (IRI) concentrations attained following oral ingestion of 100 gm of glucose differed significantly in the two groups of diabetics, suggesting that they may represent distinct disorders. There was more than a threefold difference in the maximal plasma IRI response between the normal Navajo and normal Amish, indicating that there is marked ethnic variability in the normal insulin response to an orally given glucose load.

Effect of feeding on hormonal responses to 2-deoxy-D-glucose in conscious monkeys.

2-Deoxy-D-glucose (2-DG) was injected intravenously (300 mg/kg) into 6 conscious monkeys adapted to chronic restraint in primate chairs. In 10 experiments, chow and water were provided to the monkeys after the injection of 2-DG. In 16 experiments, chow and water were withheld. Feeding did not affect themarked hyperglycemia or the increase in plasma growth hormone or 17-hydroxycorticosteroids elicited by 2-DG, but feeding markedly increased plasma immunoreactive insulin (IRI) concentrations, probably through the release of enteric stimulant(s) of insulin secretion. (Endocrinology85: 963, 1969)

Plasma glucose levels in normal and adrenalectomized mice treated with streptozotocin and nicotinamide.

Serial alterations in blood glucose of normal and adrenalectomized mice following the administration of a diabetogenic dose of streptozotocin have been compared with those of similar mice pretreated with nicotinamide. An initial hyperglycemic phase, one to three hours post-injection, was observed with both streptozotocin and nicotinamide treated mice, and was drug related. In the case of streptozotocin the early elevation in blood sugar was not dependent on the presence of the adrenal gland. An initial hyperglycemic phase was recorded in fed adrenalectomized mice but was eliminated in fasted adrenalectomized mice because of decreased liver glycogen. A hypoglycemic phase at seven hours was observed with streptozotocin treatment. This was associated with a seven-fold increase in plasma immunoreactive insulin (IKI) concentration observed in streptozotocin treated normals. By twenty-four hours the streptozotocin treated mice were permanently diabetic, and had significantly depressed pancreatic insulin concentrations, while plasma insulin was still greater than control concentrations. The nicotinamide protected group demonstrated no evidence of diabetes. The mechanism of diabeto genesis of streptozotocin differs from that of alloxan.

Insulin-secreting bronchial carcinoid tumor with widespread metastases

This is a report of a twenty-three year old woman with severe hypoglycemia, elevated plasma immunoreactive insulin concentrations and widespread malignancy. A bronchial carcinoid tumor was identified as the primary neoplasm and increased concentrations of immunoreactive insulin were found in the bronchial tumor and its metastases. This is believed to be the first reported case of a hypoglycemia-producing bronchial carcinoid tumor associated with increased plasma immunoreactive insulin. Diazoxide administration produced no beneficial effect in this patient.

Influence of Cortisol on Plasma Insulin in the Sheep

Daily injection of a group of sheep with 75 mg. cortisol acetate (1.2 mg. per kilogram body weight) resulted in hyperglycemia and in a marked increase in plasma immunoreactive insulin concentrations. Doubling the dose of cortisol after fourteen days did not result in further increases in glucose or insulin concentrations, but the elevated levels were maintained throughout treatment. Intravenous glucose tolerance tests using 0.1 gm. glucose per kilogram body weight showed that the rate of glucose removal was decreased and the increment in plasma insulin concentration reduced by cortisol treatment. With a larger glucose load (0.5 gm. per kilogram body weight) there was an exaggerated insulin response to the increased plasma glucose level during the first period of cortisol treatment, but in the second period the response was no greater than that in the control period. Changes in plasma glucose and insulin concentrations in the eight hours following feeding were much exaggerated during cortisol treatment, even though there is little absorption of glucose from the digestive tract in this species. In the absence of evidence of increased glucose turnover in the sheep during cortisol-induced hyperglycemia, the changes are indicative of marked impairment of peripheral glucose metabolism and antagonism of insulin action by cortisol in this species.