The effect of glucagon (50 ng/kg/min) on arterial glycerol concentration and net splanchnic production of total ketones and glucose was studied after an overnight fast in four normal and five insulin-dependent diabetic men. Brachial artery and hepatic vein catheters were inserted and splanchnic blood flow determined using indocyanine green. The glucagon infusion resulted in a mean circulating plasma level of 4,420 pg/ml.

In the normal subjects, the glucagon infusion resulted in stimulation of insulin secretion indicated by rising levels of immunoreactive insulin and C-peptide immunoreactivity. Arterial glycerol concentration (an index of lipolysis) declined markedly and net splanchnic total ketone production was virtually abolished. In contrast, the diabetic subjects secreted no insulin (no rise in C-peptide immunoreactivity) in response to glucagon. Arterial glycerol and net splanchnic total ketone production in these subjects rose significantly (P=<0.05) when compared with the results in four diabetics who received a saline infusion after undergoing the same catheterization procedure.

Net splanchnic glucose production rose markedly during glucagon stimulation in the normals and diabetics despite the marked rise in insulin in the normals. Thus, the same level of circulating insulin which markedly suppressed lipolysis and ketogenesis in the normals failed to inhibit the glucagon-mediated increase in net splanchnic glucose production.

It is concluded (a) that glucagon at high concentration is capable of stimulating lipolysis and ketogenesis in insulin-deficient diabetic man; (b) that insulin, mole for mole, has more antilipolytic activity in man than glucagon has lipolytic activity; and (c) that glucagon, on a molar basis, has greater stimulatory activity than insulin has inhibitory activity on hepatic glucose release.

/pdf/effects-of-glucagon-on-lipolysis-and-ketogenesis-in-normal-46cjfepsrt.pdf

Effects of Glucagon on Lipolysis and Ketogenesis in Normal and Diabetic Men

A method for determination of free fatty acids in serum.

Extraction and fractionation of the media of the thoracic aorta

The finding of high plasma free fatty acid (FFA) levels in cirrhotic patients has been attributed either to decreased hepatic clearance or to enhanced fat mobilization. To better clarify these hypotheses, total and individual FFA and glycerol levels were determined in 21 cirrhotic patients with different degrees of hepatocellular damage (evaluated by liver function tests), portal hypertension (evaluated by endoscopy and clinical signes), and nutritional status (evaluated by anthropometric and biohumoral parameters) and in 10 age- and sex-matched healthy subjects. Glucose tolerance and insulin and glucagon levels were determined in all individuals. Well-nourished and malnourished patients were identified within the cirrhotic group. Plasma FFA and glycerol concentrations were well correlated (r = 0.47, P < 0.05), levels being significantly higher in cirrhotic individuals than in controls (746.6 ± 46.29 SE v 359.22 ± 40.82 μmol/L, P < 0.001 for plasma FFA; 150.1 ± 3.12 v 82.5 ± 9.2 μmol/L, P < 0.01) for glycerol). Plasma FFA and glycerol showed no correlation with the liver function test results or portal hypertension parameters. Interestingly, plasma levels of FFA and glycerol were influenced by the nutritional status, significantly higher FFA levels being observed in the well-nourished than in the malnourished patients (842.5 ± 47.5 v 563.4 ± 78 μmol/L, P < 0.005). Furthermore, a positive correlation was found between plasma glycerol level and percentage of triceps skinfold (r = 0.45, P < 0.05). No correlation was found between plasma levels of FFA or glycerol and glucose tolerance, insulin and glucagon. So far the individual FFA patterns are concerned, a significant percentage decrease was observed in palmitic and stearic acid levels and a significant percentage increase in palmitoleic and oleic acid levels in the cirrhotic group, no difference being found between well-nourished and malnourished patients. In conclusion, the high plasma FFA and glycerol levels in patients with liver cirrhosis do not appear to depend on the degree of liver damage or portal hypertension, but rather are due to enhanced lipolysis. Fat mobilization appears to decrease as malnutrition advances.

Total and individual free fatty acid concentrations in liver cirrhosis.

The chlorophyll metabolite phytanic acid is a natural rexinoid--potential for treatment and prevention of diabetes.

Blood fatty acids in various pathologic conditions. Apropos of 156 observations

Variations quantitatives et qualitatives des acides gras non estérifiés et des triglycérides circulants induites par le glucagon

Nouvelle méthode pour la détermination rapide et précise de la lipase sérique

La captation myocardique des acides gras libres chez l'homme: étude des acides gras individuels et action de divers agents pharmacodynamiques

Influence du glucose sur la composition des acides gras non estérifiés du plasma humain normal

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