Role of glucagon in disposal of an amino acid load

Boden, Guenther; Tappy, Luc; Jadali, Fayegh; Hoeldtke, Robert D.; Rezvani, Iraj; Owen, Oliver E.

doi:10.1152/ajpendo.1990.259.2.e225

Cited by 34 publications

(38 citation statements)

References 32 publications

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“…Moreover, this relative hyperglucagonaemia has been shown to participate in the development of hyperglycaemia [12]. We have also shown that amino acids increase EGP when infused together with exogenous glucose [13] or during hyperinsulinaemic clamps and that amino acid-induced glucagon secretion plays a pivotal role in stimulating EGP in this condition [14]. We therefore assessed the effect of hyperglucagonaemia on fructose-induced gluconeogenesis and on EPG in lean healthy subjects.…”

Section: Discussionmentioning

confidence: 98%

Effects of ingested fructose and infused glucagon on endogenous glucose production in obese NIDDM patients, obese non-diabetic subjects, and healthy subjects

et al. 1996

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SummaryIncreased endogenous glucose production (EGP) and gluconeogenesis contribute to the patho-genesis of hyperglycaemia in non-insulin-dependent diabetes mellitus (NIDDM). In healthy subjects, however, EGP remains constant during administration of gluconeogenic precursors. This study was performed in order to determine whether administration of fructose increases EGP in obese NIDDM patients and obese non-diabetic subjects. Eight young healthy lean subjects, eight middle-aged obese NIDDM patients and seven middle-aged obese non-diabetic subjects were studied during hourly ingestion of 13 C fructose (0.3 g · kg fat free mass -1 · h -1 ) for 3 h. Fructose failed to increase EGP (measured with 6,6 2 H glucose) in NIDDM (17.7 ± 1.9 µmol · kg fat free mass -1 · min -1 basal vs 15.9 ± 0.9 after fructose), in obese non-diabetic subjects (12.1 ± 0.5 basal vs 13.1 ± 0.5 after fructose) and in lean healthy subjects (13.3 ± 0.5 basal vs 13.8 ± 0.6 after fructose) although 13 C glucose synthesis contributed 73.2 % of EGP in lean subjects, 62.6 % in obese non-diabetic subjects, and 52.8 % in obese NIDDM patients. Since glucagon may play an important role in the development of hyperglycaemia in NIDDM, healthy subjects were also studied during 13 C fructose ingestion + hyperglucagonaemia (232 ± 9 ng/l) and during hyperglucagonaemia alone. EGP increased by 19.8 % with ingestion of fructose + glucagon (p < 0.05) but remained unchanged during administration of fructose or glucagon alone. The plasma 13 C glucose enrichment was identical after fructose ingestion both with and without glucagon, indicating that the contribution of fructose gluconeogenesis to the glucose 6-phosphate pool was identical in these two conditions. We concluded that during fructose administration: 1) gluconeogenesis is increased, but EGP remains constant in NIDDM, obese non-diabetic, and lean individuals; 2) in lean individuals, both an increased glucagonaemia and an enhanced supply of gluconeogenic precursors are required to increase EGP; this increase in EGP occurs without changes in the relative proportion of glucose 6-phosphate production from fructose and from other sources (i. e. glycogenolysis + gluconeogenesis from non-fructose precursors). [Diabetologia (1996) Abbreviations: EGP, Endogenous glucose production ; CHO, carbohydrate ; APE, atom percent excess ; GRd, glucose rate of disappearance ; FFM, fat-free mass.In healthy human subjects and in normal dogs, endogenous glucose production (EGP) has been shown not to rise when gluconeogenic substrates are infused and gluconeogenesis is increased [1][2][3][4][5]. This constancy of EGP was also observed during infusions of lactate [2] or fructose [5] when insulin and glucagon were maintained constant by infusions of somatostatin, insulin and glucagon, indicating autoregulation. The mechanisms responsible for this autoregulation of EGP may involve inhibition of gluconeogenesis from endogenous substrates [3] and/or of glucogenolysis [2] and stimulation of glycogen synthesis [5]. In non-insulin-depende...

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Section: Discussionmentioning

confidence: 98%

Effects of ingested fructose and infused glucagon on endogenous glucose production in obese NIDDM patients, obese non-diabetic subjects, and healthy subjects

et al. 1996

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“…These latter changes, though statistically significant, were ofminimal magnitude and unlikely to be consequential in the present experiments. To avoid the possibility that changes of fetal glucagon concentration that may occur with fetal insulin infusion (33) would independently affect protein metabolism (34,35), we infused somatostatin to minimize endogenous glucagon release and infused exogenous glucagon to maintain normal glucagon concentrations throughout the experiments. Somatostatin also decreases fetal growth hormone secretion (36), but this fact should not influence the present study for two reasons.…”

Section: Discussionmentioning

confidence: 99%

Effects of insulin on ovine fetal leucine kinetics and protein metabolism.

Milley¹

1994

J. Clin. Invest.

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Fetuses of eight pregnant ewes (114-117 d of gestation) were used to study whether fetal insulin concentration affects fetal protein accretion and, if so, whether such changes are caused by effects on protein synthesis or protein breakdown. Fetal leucine kinetics were measured by infusion of I1-'4Clleucine during each of three protocols: (I) low vs. normal insulin concentration; (II) low vs. high insulin concentration; and (III) low vs. high insulin concentration during amino acid infusion to keep leucine concentration constant. Fetal leucine concentration (233±20 vs. 195±18 ,uM)

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“…This is the case either after the ingestion of a large protein meal (or an amino acid infusion), when exogenous amino acids need to be metabolized and excess nitrogen excreted, or during periods of fast, when endogenous amino acids are used for gluconeogenesis. Actually, gluconeogenesis and ureagenesis are always linked (1), in order to ensure an appropriate disposal of the amine groups when the carbon chains of amino acids enter carbohydrate metabolism (2)(3)(4).…”

Section: Introductionmentioning

confidence: 99%

Cyclic AMP is a hepatorenal link influencing natriuresis and contributing to glucagon-induced hyperfiltration in rats.

Ahloulay¹,

Déchaux²,

Hassler³

et al. 1996

J. Clin. Invest.

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The effects of glucagon (G) on proximal tubule reabsorption (PTR) and GFR seem to depend on a prior action of this hormone on the liver resulting in the liberation of a mediator and/or of a compound derived from amino acid metabolism. This study investigates in anesthetized rats the possible contribution of cAMP and urea, alone and in combination with a low dose of G, on phosphate excretion (known to depend mostly on PTR) and GFR. After a 60-min control period, cAMP (5 nmol/min ϫ 100 grams of body weight [BW]) or urea (2.5 mol/min ϫ 100 grams BW) was infused intravenously for 200 min with or without G (1.2 ng/min ϫ 100 grams BW, a physiological dose which, alone, does not influence PTR or GFR). cAMP increased markedly the excretion of phosphate and sodium ( ϩ 303 and ϩ 221%, respectively, P Ͻ 0.01 for each) but did not alter GFR. Coinfusion of cAMP and G induced the same tubular effects but also induced a 20% rise in GFR ( P Ͻ 0.05). Infusion of urea, with or without G, did not induce significant effects on PTR or GFR. After G infusion at increasing doses, the increase in fractional excretion of phosphate was correlated with a simultaneous rise in plasma cAMP concentration and reached a maximum for doubling of plasma cAMP. These results suggest that cAMP, normally released by the liver into the blood under the action of G, ( a ) is probably an essential hepatorenal link regulating the intensity of PTR, and ( b ) contributes, in conjunction with specific effects of G on the nephron, to the regulation of GFR. ( J. Clin. Invest. 1996. 98: 2251-2258.)

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Role of glucagon in disposal of an amino acid load

Cited by 34 publications

References 32 publications

Effects of ingested fructose and infused glucagon on endogenous glucose production in obese NIDDM patients, obese non-diabetic subjects, and healthy subjects

Effects of ingested fructose and infused glucagon on endogenous glucose production in obese NIDDM patients, obese non-diabetic subjects, and healthy subjects

Effects of insulin on ovine fetal leucine kinetics and protein metabolism.

Cyclic AMP is a hepatorenal link influencing natriuresis and contributing to glucagon-induced hyperfiltration in rats.

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