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Biomedical subjects

P Felig

Publications and source records attributed to P Felig.

At least 127 records · Page 7Linked to original sources
PubMed1978

Hyperglucagonemia in cirrhosis: altered secretion and sensitivity to glucagon.

Plasma glucagon concentration was elevated 2- to 6-fold in cirrhotic patients with spontaneous portal systemic shunting or surgically induced portacaval anastomosis but was comparable to controls in cirrhotics without portal-systemic shunting. The metabolic clearance rate of glucagon (mol wt 3500) was normal in all of the cirrhotic groups, but the estimated basal systemic delivery rate of glucagon was increased 2- to 6-fold in the hyperglucagonemic patients. The blood glucose response to infusion of glucagon (3 ng per kg per min) was reduced in the cirrhotics with portal-systemic shunting or portacaval anastomosis, and correlated inversely with the delivery rate of endogenous glucagon. Administration of ammonium chloride (3 g) failed to elevate plasma glucagon concentration. It is concluded that hyperglucagonemia in cirrhosis is a consequence of hypersecretion rather than decreased hormonal catabolism. A negative feedback signal may exist between hepatic sensitivity to glucagon and the secretion of this hormone.

Adult↗
PubMed1977

Metabolic effects of somatostatin in maturity-onset diabetes.

To examine the effects of prolonged infusions of somatostatin in maturity-onset diabetes, we administered five-hour infusions to eight patients. This infusion resulted in a 45 to 55 per cent decline in plasma insulin and glucagon. Plasma glucose initially fell by 20 to 25 mg per 100 ml, but later rose despite continuing hypoglucagonemia. After five hours, plasma glucose concentration was 40 to 50 mg per 100 ml higher than that observed with saline infusion (P less than 0.001). The degree of hyperglycemia and plasma insulin levels correlated inversely at completion of the infusion (P less than 0.01). In addition, somatostatin resulted in a fivefold increase in beta-hydroxybutyrate and a 40 to 45 per cent rise in branched-chain amino acids (P less than 0.005). Our findings suggest that glucagon is not essential for the development and maintenance of fasting hyperglycemia. Furthermore, accentuation by somatostatin of hyperglycemia, hyperketonemia and hyperaminoacidemia in maturity-onset diabetes argues against its use in patients with residual insulin secretion.

Adult↗
PubMed1977

Influence of physiologic hyperglucagonemia on urinary glucose, nitrogen, and electrolyte excretion in diabetes.

To evaluate the effect of physiologic hyperglucagonemia on nitrogen and glucose metabolism and on urinary electrolyte excretion, pancreatic glucagon was administered as a continuous 3-day infusion to three adult-onset non-insulin-dependent diabetics and two insulin-treated juvenile diabetics while on a constant dietary intake. The glucagon infusion resulted in increases in plasma glucagon which were 4-6 fold greater than control values. Despite prolonged hyperglucagonemia, urinary glucose excretion was unchanged. Similarly, urinary urea nitrogen and total nitrogen excretion were not altered by glucagon administration. Urinary sodium tended to rise, albeit not significantly (p less than .01), on the first infusion day, but later declined to control values despite increasing plasma glucagon concentrations. Urinary chloride, potassium, calcium, phosphorus excretion remained unchanged. We conclude that continuous physiologic increments in plasma glucagon do not enhance glycosuria or increase protein catabolism and ureagenesis in diabetes when insulin is available. The augmented protein catabolism and glucogenesis that accompany diabetic ketoacidosis cannot be explained primarily on the basis of hyperglucagonemia.

Adult↗
PubMed1977

Renal extraction of glucagon in rats with normal and reduced renal function.

To examine the role of the kidney in the mechanism of impaired metabolic clearance of glucagon in renal failure, the renal handling of endogenous pancreatic glucagon was studied in rats with normal renal function and rats with renal insufficiency produced by 70% surgical ablation. Mean +/- SE renal extraction of glucagon in animals with normal renal function was 39 +/- 5%. Urinary losses of glucagon accounted for less than 2% of renal extraction. In contrast, in the animals with renal insufficiency (glomerular filtration rate reduced to one-third of normal), arterial glucagon increased 40% and renal extraction and extraction rate per gram kidney weight of glucagon were negligible, despite filtered loads of 204 +/- 42 pg/min per g kidney wt. These findings indicate a major role of the kidney in the metabolic clearance of glucagon under normal conditions and suggest that during renal insufficiency elevated plasma levels of glucagon occur, at least in part, as a result of a decreased renal turnover of the hormone.

Animals↗
PubMed1977

Influence of somatostatin on splanchnic glucose metabolism in postabsorptive and 60-hour fasted humans.

Cyclic somatostatin was administered intravenously (10 mug/min for 60 min) to 10 healthy overnight fasted (postabsorptive) subjects and to 5 healthy 60-h fasted subjects. In both groups, arterial insulin and glucagon fell 50% and splanchnic release of these hormones was inhibited. In the overnight fasted subjects splanchnic glucose output fell 70%, splanchnic uptake of lactate and pyruvate was unchanged, alanine uptake fell by 25%, and glycerol uptake rose more than twofold in parallel with an increase in arterial glycerol. In the 60-h fasted group splanchnic glucose output was less than 40% of that observed in the overnight fasted subjects. Somatostatin led to a further decrease (--70%) in glucose production. Splanchnic uptake of lactate and pyruvate fell by 30-40%, amino acid uptake was unchanged, while uptake of glycerol rose fivefold. Total uptake of glucose precursors thus exceeded the simultaneous glucose output by more than 200%. Splanchnic uptake of FFA rose fourfold during somatostatin while output of beta-hydroxybutyrate increased by 75%. Estimated hepatic blood flow fell 25-35% and returned to base line as soon as the somatostatin infusion ended. It is concluded that (a) somatostatin-induced hypoglucagonemia results in inhibition of splanchnic glucose output in glycogen-depleted, 60-h fasted subjects as well as in postabsorptive subjects, indicating an effect of glucagon on hepatic gluconeogenesis as well as glycogenolysis; (b) the glucagonsensitive step(s) in gluconeogenesis affected by somatostatin involves primarily intra-hepatic disposal rather than net hepatic uptake of glucose precursors; (c) splanchnic uptake of fatty acids and ketone output are increased in the face of combined insulin and glucagon deficiency; and (d) diminished splanchnic blood flow may contribute to some of the effects of somatostatin on splanchnic metabolism.

Adult↗
PubMed1977

Glucagon and insulin binding to liver membranes in a partially nephrectomized uremic rat model.

To investigate the role of glucagon and insulin receptor binding in the glucagon hypersensitivity and insulin resistance which characterize the glucose intolerance of uremia, liver plasma membranes were prepared from control rats (blood urea nitrogen [BUN] 15+/-1 mg/100 ml, creatinine 0.7+/-0.2 mg/100 ml), and from 70% nephrectomized rats (BUN 30+/-2 mg/100 ml, creatinine 2.2+/-0.2 mg/100 ml), and from 90% nephrectomized rats (BUN 46+/-3 mg/100 ml, creatinine 4.20+/-0.7 mg/100 ml), 4 wk after surgery. As compared to controls, the 90% nephrectomized rats had significantly higher levels of plasma glucose (95+/-4 vs. 125+/-11 mg/100 ml), plasma insulin (28+/-9 vs. 52+/-11 muU/ml), and plasma glucagon (28+/-5 vs. 215+/-18 pg/ml). Similar, but less marked, elevations were observed in the 70% nephrectomized animals. In liver plasma membranes from nephrectomized rats, specific binding of (125)I-glucagon was increased by 80-120%. Furthermore, glucagon (2 muM)-stimulated adenylate cyclase activity in nephrectomized rats was twofold higher than in controls. In contrast, fluoridestimulated adenylate cyclase activity was similar in both groups of rats. In marked contrast to glucagon binding, specific binding of (125)I-insulin to liver membranes from nephrectomized rats was reduced by 40-50% as compared to controls. Data analysis suggested that the changes in both glucagon and insulin binding are a consequence of alterations in binding capacity rather than changes in affinity. Liver plasma membranes from nephrectomized rats degraded (125)I-glucagon and (125)I-insulin to the same extent as control rats. THESE RESULTS DEMONSTRATE THAT: (a) the 70 and 90% nephrectomized rats simulate the hyperglycemia, hyperinsulinemia, and hyperglucagonemia observed in clinical uremia; (b) in these animals specific binding of glucagon to liver membranes is increased and is accompanied by higher glucagon-stimulated adenylate cyclase activity; and (c) specific binding of insulin is markedly decreased. These findings thus provide evidence of oppositely directed, simultaneous changes in glucagon and insulin receptor binding in partially nephrectomized rats. Such changes may account for the hypersensitivity to glucagon and may contribute to resistance to insulin observed in the glucose intolerance of uremia.

Adenylyl Cyclases↗
PubMed1977

Influence of glucagon replacement on the hyperglycemic and hyperketonemic response to prolonged somatostatin infusion in normal man.

Somatostatin was infused for 6 h into seven normal subjects with and without a replacement dose of glucagon. The addition of glucagon to somatostatin resulted in a 30-40% rise in plasma glucagon, whereas plasma insulin declined by 40-50% in both treatment groups. Plasma glucose and glucose production initially increased 2-fold with glucagon replacement, and subsequently declined by 2-3 h to levels comparable to those observed with somatostatin alone. After 6 h plasma glucose and glucose kinetics were no different whether or not glucagon was present. The rise in blood ketones after somatostatin was not exaggerated by glucagon replacement. We conclude that glucagon lack is not a modifying factor in the late hyperglycemic and hyperketonemic response to prolonged infusions of somatostatin.

Adult↗
PubMed1977

Amino acid and protein metabolism in diabetes mellitus.

In normal man, the fasting state is characterized by release of alanine and glutamine from muscle and in situ muscle catabolism of branched chain amino acids (lecucine, isoleucine, and valine). The alanine released by muscle is utilized by the liver for gluconeogenesis. Muscle nitrogen repletion occurs during protein feeding primarily by means of selective hepatic escape and muscle uptake of branched chain amino acids in ingested protein. In the diabetic, amino acid catabolism is exaggerated in the fasting state as reflected by increased uptake of alanine by the liver for gluconeogenesis and accelerated branched chain amino acid catabolism in muscle. After protein feeding, uptake of branched chain amino acids by muscle is reduced and these amino acids accumulate in increased amounts in arterial blood. Protein feeding also exaggerates the hyperglycemia of diabetes by causing an increase in hepatic glucose production. Diabetes is thus characterized by accelerated protein catabolism during fasting as well as diminished nitrogen repletion and hyperglycemia after protein feeding. The hyperketonemia of diabetes may however, have a restraining influence on protein catabolism thereby reducing alanine availability for gluconeogenesis.

Alanine↗