Horm. Metab. Res. 9 (977) 253-257 @ Georg Thieme Verlag Stuttgart
The Effect of Short Term Physiological Elevations of Plasma Glucagon Concentration on Plasma Triglyceride Concentration in Normal and Diabetic Man D.S. Schade and R.P. Eaton
Summary To explore the effect of physiological elevations of glucagon on plasma triglyceride concentration, glucagon was infused for thirty minutes at 3.0 ng/kg/min into both normal and insulin dependent diabetic subjects. The effects of this hormonal infusion on plasma triglyceride, free fatty acids, glucose, and insulin were compared to a control saline infusion study. A differential effect of glucagon on plasma triglyceride concentration between normal and diabetic subjects was observed. In normal subjects, glucagon infusion was accompanied by a concomitant increase in endogenous insulin secretion and free fatty acid levels, and no observable effect on circulating plasma triglyceride concentration. In contrast, in diabetic subjects, no change in insulin or free fatty acid concentration occurred during glucagon infusion and circulating plasma triglyceride concentration declined after twenty minutes of hormone infusion. These results suggest that plasma triglyceride concentration may be modulated, at least in part, by alterations in circulating plasma glucagon in concert with insulin secretion and free fatty acid availability in man. Key-Words: Triglyceride - Glucagon - Free Fatty Acid Insulin
Introduction During the past decade, much evidence has accrued supporting the concept the acute pharmacological elevations of plasma glucagon concentration resuIt in significant alterations of plasma triglyceride concentration (Eaton, Schade and Conway 1974). This hormonal effect has been documented both in vitro (Eaton 1973) and in vivo (Schade and Eaton 1975, Aubry, Mancel and Davignon 1974). However, in our glucagon dose response studies in man, two observations emerged which suggested that the triglyceride response to this hormone may be modified by the experimental setting (Schade and Eaton 1975). First, at the lowest dosage of administered glucagon, a prompt elevation of plasma triglyceride concentration was observed. At progressively higher dosages of hormone, the rise in triglyceride concentration no longer occurred, while at still higher dosages an actual reduction in triglyceride levels was observed. Secondly, glucagon injection resuIted in an exaggerated triglyceride lowering effect in the insulin Received: 12 Aug. 1976
Accepted: 10 Jan. 1977
dependent diabetic subject in whom the counter-regulatory actions of glucagon stimulated insulin secretion were not present (Schade and Eaton 1975). Since these studies consisted of a bolus injection of glucagon with rapid loss of hormone concentration from plasma (t 1/2 ~ 5 minutes), we designed the present studies to ex amine the effects of sustained physiological elevations of plasma glucagon on endogenous triglyceride concentration.
Methods Five normal (three females, two males) and five insulin dependent diabetic subjects (two females, three males) were studied, all within ± 5% of odeal body weight. All subjects 200 mg/dl, triglyceride 125 were eulipenic {cholesterol rng/dl, and in good general health. Ages range from 22 to 36 years. Normal subjects were non-diabetic by U.S.P.H.S. criteria (O'Sullivan and Mahan 1968). All diabetic subjects had a documented medical history of ketoacidosis and were receiving between 38 and 54 units of UIOO NPH insulin each morning. Diabetic subjects were following standard American Diabetes Association diets prescribed by their personal physician and non-diabetic subjects were following regular weight maintaining diets containing at least 250 gm of carbohydrate per day.
.1. In contrast, in the diabetic subjects the glucagon infusion resulted in an initial rise with a subsequent decline in plasma triglyceride concentration. Analysis of the sequential change in triglyceride concentration in the diabetic subjects demonstrated that triglyceride concentration declined by 14.4 ± 7 mgjdl from twenty to thirty minutes post initiation of glucagon infusion. This decline in concentration was significantly different from the positive change in the saline control study (+ 0.2 ± 3.4 mgjdl) during the same time period (p < .05).
Glucagon and Plasma Triglycerides
255
minutes of initiating the infusion suggesting that high physiological circulating concentrations of glucagon were present for at least 20 minutes of the study.
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The Effect of Short Term Physiological Elevations of Plasma Glucagon Concentration on Plasma Triglyceride Concentration in Normal and Diabetic Man D.S. Schade and R.P. Eaton
Summary To explore the effect of physiological elevations of glucagon on plasma triglyceride concentration, glucagon was infused for thirty minutes at 3.0 ng/kg/min into both normal and insulin dependent diabetic subjects. The effects of this hormonal infusion on plasma triglyceride, free fatty acids, glucose, and insulin were compared to a control saline infusion study. A differential effect of glucagon on plasma triglyceride concentration between normal and diabetic subjects was observed. In normal subjects, glucagon infusion was accompanied by a concomitant increase in endogenous insulin secretion and free fatty acid levels, and no observable effect on circulating plasma triglyceride concentration. In contrast, in diabetic subjects, no change in insulin or free fatty acid concentration occurred during glucagon infusion and circulating plasma triglyceride concentration declined after twenty minutes of hormone infusion. These results suggest that plasma triglyceride concentration may be modulated, at least in part, by alterations in circulating plasma glucagon in concert with insulin secretion and free fatty acid availability in man. Key-Words: Triglyceride - Glucagon - Free Fatty Acid Insulin
Introduction During the past decade, much evidence has accrued supporting the concept the acute pharmacological elevations of plasma glucagon concentration resuIt in significant alterations of plasma triglyceride concentration (Eaton, Schade and Conway 1974). This hormonal effect has been documented both in vitro (Eaton 1973) and in vivo (Schade and Eaton 1975, Aubry, Mancel and Davignon 1974). However, in our glucagon dose response studies in man, two observations emerged which suggested that the triglyceride response to this hormone may be modified by the experimental setting (Schade and Eaton 1975). First, at the lowest dosage of administered glucagon, a prompt elevation of plasma triglyceride concentration was observed. At progressively higher dosages of hormone, the rise in triglyceride concentration no longer occurred, while at still higher dosages an actual reduction in triglyceride levels was observed. Secondly, glucagon injection resuIted in an exaggerated triglyceride lowering effect in the insulin Received: 12 Aug. 1976
Accepted: 10 Jan. 1977
dependent diabetic subject in whom the counter-regulatory actions of glucagon stimulated insulin secretion were not present (Schade and Eaton 1975). Since these studies consisted of a bolus injection of glucagon with rapid loss of hormone concentration from plasma (t 1/2 ~ 5 minutes), we designed the present studies to ex amine the effects of sustained physiological elevations of plasma glucagon on endogenous triglyceride concentration.
Methods Five normal (three females, two males) and five insulin dependent diabetic subjects (two females, three males) were studied, all within ± 5% of odeal body weight. All subjects 200 mg/dl, triglyceride 125 were eulipenic {cholesterol rng/dl, and in good general health. Ages range from 22 to 36 years. Normal subjects were non-diabetic by U.S.P.H.S. criteria (O'Sullivan and Mahan 1968). All diabetic subjects had a documented medical history of ketoacidosis and were receiving between 38 and 54 units of UIOO NPH insulin each morning. Diabetic subjects were following standard American Diabetes Association diets prescribed by their personal physician and non-diabetic subjects were following regular weight maintaining diets containing at least 250 gm of carbohydrate per day.
.1. In contrast, in the diabetic subjects the glucagon infusion resulted in an initial rise with a subsequent decline in plasma triglyceride concentration. Analysis of the sequential change in triglyceride concentration in the diabetic subjects demonstrated that triglyceride concentration declined by 14.4 ± 7 mgjdl from twenty to thirty minutes post initiation of glucagon infusion. This decline in concentration was significantly different from the positive change in the saline control study (+ 0.2 ± 3.4 mgjdl) during the same time period (p < .05).
Glucagon and Plasma Triglycerides
255
minutes of initiating the infusion suggesting that high physiological circulating concentrations of glucagon were present for at least 20 minutes of the study.
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