Fasting Immunoreactive Glucagon Research Articles

Plasma levels of glucagon-like polypeptides in patients with esophagoplasty.

Seven patients with interposition of a jejunal tract between the esophagus and stomach or duodenum (EP group) and ten healthy normal volunteers have been submitted to an oral glucose load (OGTT) to clarify the significance of glucagon-like polypeptides (GLI) induced by glucose in carbohydrate metabolism. Blood glucose (BG) and GLI plasma levels were significantly higher in the EP group than in the normal one (p less than 0.01), respectively 30, 60, 90 min for BG and during all the test for GLI. The fasting immunoreactive glucagon (IRG) plasma levels were significantly lower in patients than in normals (p less than 0.05) whereas a marked and significant increase was observed in the EP group (p less than 0.01) from 90 to 240 min. The precocious stimulation of jejunal mucosa and the rapid intestinal transit which occur in these patients may explain the elevated GLI (probably glicentin) plasma levels. The rise in IRG plasma levels might be due to the enzymatic transformation of glicentin. The role of these types of glucagon on carbohydrate metabolism is still to be fully clarified.

Studies on plasma glucagon concentration in maturity-onset diabetics with autonomic neuropathy.

The mean fasting plasma immunoreactive glucagon (IRG) concentration in 25 non-insulin-dependent, maturity-onset diabetics (MODs) was 15.4 ± 3.1 pmol/L, which was not significantly different from the 16.8 ± 2.4 pmol/L in 17 normal controls of similar age. However, in seven MODs with autonomic neuropathy (AN) the mean fasting IRG concentration of 44.7 ± 4.4 was significantly greater than the 17.4 ±1.3 pmol/L in 18 MODs without neuropathy and compared with controls. We, therefore, investigated IRG concentrations in five age-matched, non-insulin-dependent MODs with AN and five without it. Plasma IRG concentrations were measured in the basal state on three separate occasions and in response to insulin and to a mixed meal. Fasting or basal IRG concentrations were measured in the morning with and without a preceding 12-h insulin infusion to determine the effects of reduction in fasting plasma glucose concentrations and after 12 h of nasogastric aspiration to exclude continued stimulation caused by delayed gastric emptying. In the select group of Subjects the mean basal plasma IRG concentration was raised above the normal in diabetics with AN (49.4 ± 5.1) and was 16.2 ± 2.1 in diabetics without AN, which was within normal limits. Neither 12 h of insulin infusion (0.5–0.8 U/h) nor 12 h of nasogastric aspiration altered basal IRG concentrations in either group. The maximum incremental IRG response to acute insulin administration (0.2 U/kg) in diabetics with AN was 6.8 ± 3.9, which was significantly impaired compared with 24.9 ± 4.8 in nine MODs without AN and with 26.3 ± 6.7 in five normal controls. The maximum increment in IRG response to acute insulin administration in diabetics with AN rose significantly to 32.8 ± 12.9 after 12 h of insulin infusion. Although the maximum IRG responses to a mixed meal were higher in both diabetic groups than in the normal controls, there was a delayed initial rise and persistent elevation in diabetics with AN. We suggest that (1) basal IRG concentrations may be dependent on the integrity of the autonomic nervous system in MODs; (2) MODs without AN seem to have a normal response to insulin-induced hypoglycemia, whereas in MODs with AN the response is impaired and can be corrected by an adequate degree of both insulinization and reduction in fasting blood glucose concentration; and (3) the maximum IRG response to a mixed meal is exaggerated in all MODs and is not dependent on the integrity of the autonomic nervous system, although the pattern of response may be altered in the presence Of AN.

Hormonal and metabolic responses to intravenous glucose in children on regular hemodialysis ,

Blood glucose, plasma nonesterified fatty acids, amino acids, immunoreactive insulin, growth hormone, and immunoreactive glucagon responses to intravenous glucose were determined in 16 children on regular hemodialysis for chronic renal failure and nine healthy children. In the patients the fractional disappearance rate of glucose was significantly reduced, basal immunoreactive insulin was significantly raised, and while the early immunoreactive insulin response to glucose was similar in patients and controls, the late response was increased. Basal growth hormone was elevated in the patients and rose paradoxically following glucose. Fasting immunoreactive glucagon was significantly higher in the patients and was not suppressed by glucose. Plasma nonesterified fatty acid levels were lower in the patients and fell more markedly after glucose. Alanine levels, which were significantly raised in those with poor glucose tolerance, fell to normal after glucose and did not vary in those with more normal glucose tolerance. It is speculated that the metabolic and hormonal alterations may be interrelated and result from failure of normal glucose utilization.

Glucose-Lowering Effect of Insulin by Different Routes in Obese and Lean Nonketotic Diabetic Patients*

The absorption of insulin and its glucose-lowering effect were compared after the administration of crystalline insulin by sc, im, and iv routes in 29 obese and 10 lean nonketotic diabetic patients, none of whom had consciously received insulin previously. Each of the patients received insulin in a dose of 0.1 U/kg BW by the im, sc, and iv routes in a randomized fashion on 3 different days. Plasma glucose, immunoreactive insulin (IRI), and immunoreactive glucagon (IRG) were measured at intervals over the first 4 h. The t1/2 (mean +/- SEM) after iv administration of insulin in obese and lean diabetics was, respectively, 5.3 +/- 0.2 and 4.8 +/- 0.4 min; these were not significantly different. Intravenous injection produced its highest level of IRI in 2 min in both groups. Thereafter, a rapid drop was observed with return to the basal level by 90 min. Equivalent amounts of im and sc insulin produced a maximal increase in plasma IRI at 60 min in both groups. Plasma IRI after iv insulin injection was significantly higher than after sc and im insulin injections at 10 and 20 min (P less than 0.001) and significantly lower than the im and sc groups at 60, 90, 120, 150, 180, 210, and 240 min (P less than 0.001). After iv insulin, plasma glucose at 30, 40, 50, and 60 min was significantly lower than after im and sc insulin (P less than 0.001), but over the 4-h study period, the glucose-lowering effect and the area under the curves for glucose response to IRI by the three routes were the same in both lean and obese diabetic subjects. The mean basal IRI in lean patients was 18 +/- 4 microU/ml, which was significantly lower (P less than 0.05) than in obese patients (26 +/- 2 microU/ml). No significant difference was observed in fasting IRG in lean (96 +/- 12 pg/ml) vs. obese (108 +/- 10 pg/ml) patients. No significant increase in IRG was noted with equivalent amounts of sc, im, and iv injection in the lean and obese patients. These studies demonstrated that although iv injection of insulin produces a more rapid initial decline in plasma glucose, the overall glucose-lowering effect by insulin given iv, im or sc is similar in nonketotic lean or obese diabetic subjects.

The role of glucagon deficiency in the Houssay phenomenon of dogs.

Plasma glucose, immunoreactive glucagon (IRG), and insulin were measured in hypophysectomized dogs receiving cortisol and thyroid replacement therapy. 4 wk after hypophysectomy mean fasting plasma glucose levels had declined from 90+/-2 mg/100 ml to 64+/-2; fasting and arginine-stimulated insulin and IRG levels were, respectively, approximately 50% lower and unchanged. 12 wk or more after hypophysectomy, despite lower plasma glucose levels, fasting and arginine-stimulated IRG levels were significantly below control dogs. Hypophysectomized and shamhypophysectomized dogs were subjected to total pancreatectomy. Postoperatively, in the sham-hypophysectomized, depancreatized dogs fasting glucose levels ranged from 300-500 mg/100 ml on 8-10 U/day of insulin; IRG levels averaged 215+/-29 pg/ml. The hypophysectomized, depancreatized dogs required 0-4 U/day and fasting glucose levels under 100 mg/100 ml were not uncommon, even without insulin; fasting IRG levels averaged 63+/-4 pg/ml (P < 0.001). During arginine infusion in sham-hypophysectomized, depancreatized dogs, IRG levels rose from 215+/-60 pg/ml to a peak of 404+/-112 pg/ml; in hypophysectomized, depancreatized dogs, the base line IRG averaged 44+/-8 and the peak 110+/-25 pg/ml (P < 0.05). IRG levels in the venous effluent of the gastric fundus, the major source of nonpancreatic glucagon, reached a peak of 4,898+/-959 pg/ml in the sham-hypophysectomized, depancreatized group during arginine infusion and only 219+/-128 pg/ml in the hypophysectomized, depancreatized group. In three hypophysectomized, depancreatized dogs, a replacement infusion with glucagon for 10 h promptly increased hyperglycemia by 80-180 mg/100 ml and worsened glycosuria, evidence of a hepatic response to glucagon replacement. It is concluded that hypophysectomy somehow decreased both the hypersecretion of gastric IRG and the severe hyperglycemia that otherwise follows pancreatectomy. The hypophysectomized, depancreatized animal, therefore, has combined insulin and glucagon deficiency, and the latter may contribute to reduced severity of its hyperglycemia.

Immunoreactive Glucagon (IRG) Responses to Intravenous Glucose in Prediabetes and Diabetes Among Pima Indians and Normal Caucasians

Immunoreactive glucagon (IRG) response to a 3 min iv infusion of 25 g glucose was examined in 7 nondiabetic Caucasians, 8 nondiabetic, 8 prediabetic and 16 diabetic Pima Indians to define the normal IRG response and to determine if abnormalities of IRG suppression occur in diabetic and prediabetic Pima Indians. Fasting IRG levels were similar in the 3 nondiabetic groups. In response to the glucose infusion the maximum percentage fall in plasma IRG concentration was similar in the normal Caucasians (37+/-4%) and the normal (42+/-2%) and prediabetic Indians (43+/-3%). In the diabetic Indians the relative fall was less at all sampling times than among the prediabetic or normal Indians. No evidence of any differences in IRG suppression in prediabetic and normal Indians or normal Caucasians was found. Without detectable change in insulin levels during the first 10 min following the glucose infusion, IRG levels in the diabetics fell but to a lesser degree than that in the other groups.

Carbohydrate Metabolism and Pancreatic Islet-cell Function in Thalassemia Major

To investigate the development of diabetes mellitus in patients with thalassemia major, plasma glucose and immunoreactive insulin (IRI) levels following oral glucose and intravenous tolbutamide and glucose disappearance rates following intravenous insulin were measured in 10 patients before and during five years on a high transfusion program (HTP). Plasma immunoreactive glucagon (IRG) levels following oral glucose, intravenous insulin, and arginine were measured during the sixth year. Serial percutaneous liver biopsies were performed on seven patients. The oral glucose tolerance tests (OGAT) and mean peak IRI levels were normal in nine of 10 patients before HTP. After HTP was begun a progressive deterioration of OGTT occurred despite normal IRI levels. Following tolbutamide, the mean per cent fall in plasma glucose in the patients before HTP was significantly less than in controls (p less than 0.01) and similar to that of controls during five years of HTP in spite of higher than normal peak IRI levels. Of seven survivors after six years of HTP, three had normal OGTT and four had chemical diabetes; mean peak IRI levels were normal, but fasting IRG levels were significantly higher than in controls (p less than 0.05). In all seven patients, plasma IRG failed to increase following insulin-induced hypoglycemia and was significantly higher than in controls after arginine (p less than 0.01); after oral glucose, plasma IRG fell significantly below that of fasting only in the patients with chemical diabetes (p less than 0.03). Following intravenous insulin, the mean per cent fall in glucose before and during HTP was significantly less than in controls (p less than 0.01). Hemosiderosis and cirrhosis were present in all biopsied patients. Four patients died; two had chemical and two had nonketotic insulin-dependent diabetes. These data suggest that diabetes mellitus occurs frequently in patients with thalassemia on HTP and that insulin resistance and hyperglucagonemia, possibly due to cirrhosis, are important etiologic factors.

Heterogeneity of plasma glucagon. Circulating components in normal subjects and patients with chronic renal failure.

Plasma immunoreactive glucagon (IRG) concentrations were measured in 36 patients with chronic renal failure (CRF) and 32 normal subjects. In addition, the components of circulating IRG were analyzed by gel filtration in the fasting state and after physiological stimuli. Fasting IRG was elevated (P less than 0.001) in CRF patients (534 +/- 32 pg/ml) compared with the levels found in healthy subjects (113 +/- 9 pg/ml). Oral glucose suppressed plasma IRG in CRF patients from a basal level of 568 +/- 52 to a nadir of 354 +/- 57 pg/ml (120 min). This degree of suppression (38%) was comparable to that found in normal subjects (basal = 154 +/- 20 to 100 +/- 23 pg/ml) at 120 min (35%). Intravenous infusion of arginine (250 mg/kg) resulted in a 71% rise in IRG in CRF patients and a 166% increase in normal subjects. Gel filtration of fasting plasma from CRF patients showed three major peaks. The earliest (A) was found in the void volume (mol wt greater than 40,000) and constituted 16.5 +/- 4.7% of the elution profile. The middle peak (B) eluted just beyond the proinsulin marker (approximately 9,000 mol wt) and constituted the largest proportion of the elution profile (56.5 +/- 3.4%). The third peak (C) coincided with the standard glucagon and [125I]glucagon markers (3,485 mol wt) and comprised 27.0 +/- 4% of the IRG profile. In contrast, only peaks A and C were found in fasting plasma of normal subjects (53.6 +/- 10.4% in A and 46.4 +/- 10.4 in C). After oral glucose, glucagon immunoreactivity in the 3,500 mol wt peak (C) was markedly suppressed, while the B peak in patients with CRF declined to a lesser extent. The A peak in both groups was unchanged. After an arginine infusion only the C peak increased in both groups of subjects. Gel filtration of plasma in 3 M acetic acid gave similar profiles to those obtained in glycine albumin buffer. Exposure of serum to trypsin indicated that the B and C peaks were digestible, while the A peak was resistant to the action of the enzyme. In one sample, peak C increased after a 2-h exposure of serum to trypsin. We conclude that circulating IRG in normal subjects and patients with CRF is heterogenous. The hyperglucagonemia of renal failure is largely due to an increase in IRG material of approximately 9,000 mol wt, consistent with proglucagon, although the 3,500 mol wt component is also considerably elevated (threefold). The significance of circulating IRG levels should be interpreted with caution until the relative biological activity of the three components is established.

Insulin and glucagon responses in subjects with pheochromocytoma: effect of alpha adrenergic blockade.

Impaired immunoreactive insulin (TRI) release was demonstrated in 3 of 5 subjects with pheochromocytoma. Chronic alpha adrenergic blockade with phenoxybenzamine or phentolamine corrected the insulin-releasing defect in 2 subjects but had no effect in the third. Surgical removal of the tumor resulted in complete amelioration of the impaired insulin release and improved glucose tolerance in all 3 subjects who were abnormal preoperatively. Fasting immunoreactive glucagon levels were normal in the 2 subjects in whom they were measured and neither alpha adrenergic blockage nor removal of the pheochromocytoma altered these levels. Thus, when chronic hypercatecholamine secretion in subjects with pheochromocytoma results in glucose intolerance, it is associated with inhibition of insulin release. Alpha adrenergic blockade or removal of the tumor reverses both abnormalities.