The effect of intraportal and peripheral infusions of glucagon on insulin and glucose concentrations and glucose tolerance in normal man

Holst, Jens J.; Madsen, O. Guldberg; Knop, Joachim; Schmidt, Arne

doi:10.1007/bf01234501

Cited by 23 publications

(11 citation statements)

References 16 publications

(14 reference statements)

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“…It is therefore conceivable that the inhibitory effects of epinephrine on splanchnic glucose metabolism are, in part, mediated by insufficient suppression of glucagon secretion. This possibility is, however, not supported by data indicating that marked hyperglucagonemia does not alter intravenous (36) or oral (37,38) glucose tolerance in normal humans. Studies using the double tracer technique of Radziuk et al (39) have also shown that hyperglucagonemia does not affect suppression of hepatic glucose production or the rise in total glucose uptake during glucose ingestion (4).…”

Section: Discussioncontrasting

confidence: 43%

Mechanisms of Epinephrine-induced Glucose Intolerance in Normal Humans

Saccà¹,

Vigorito²,

Cicala³

et al. 1982

J. Clin. Invest.

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A B S T R A C T To evaluate the role of the splanchnic bed in epinephrine-induced glucose intolerance, we selectively assessed the components of net splanchnic glucose balance, i.e., splanchnic glucose uptake and hepatic glucose production, and peripheral glucose uptake by combining infusion of [3-3H]glucose with hepatic vein catheterization. Normal humans received a 90-min infusion of either glucose alone (6.5 mg/kg-' per min-') or epinephrine plus glucose at two dose levels: (a) in amounts that simulated the hyperglycemia seen with glucose alone (3.0 mg/kg-' per min-'); and (b) in amounts identical to the control study. During infusion of glucose alone, blood glucose rose twofold, insulin levels and net posthepatic insulin release increased three-to fourfold, and net splanchnic glucose output switched from a net output (1.65±0.12 mg/kg-' per min-') to a net uptake (1.56±0.18). This was due to a 90-95% fall (P < 0.001) in hepatic glucose production and a 100% rise (P < 0.001) in splanchnic glucose uptake (from 0.86±0.14 to 1.71±0.12 mg/kg-' per min-1), which in the basal state amounted to 30-35% of total glucose uptake. Peripheral glucose uptake rose by 170-185% (P < 0.001). When epinephrine was combined with the lower glucose dose, blood glucose, insulin release, and hepatic blood flow were no different from values observed with glucose alone. However, hepatic glucose production fell only 40-45% (P < 0.05 vs. glucose alone) and, most importantly, the rise in splanchnic glucose uptake was totally blocked. As a result, splanchnic glucose clearance fell by 50% (P < 0.05), and net splanchnic glucose uptake did not occur. The rise in peripheral glucose uptake was also reduced by 50-60% (P < 0.001). When epinephrine was added to the same dose of glucose used in the control study, blood glucose rose twofold higher (P < 0.001). The initial rise in splanchnic glucose uptake was totally prevented; however, beyond 30 min, splanchnic glucose uptake increased, reaching levels seen in the control study when severe hyperglycemia occurred. Splanchnic glucose clearance, nevertheless, remained suppressed throughout the entire study (40%-50%, P < 0.01).It is concluded that (a) the splanchnic bed accounts for one-third of total body glucose uptake in the basal state in normal humans; (b) epinephrine markedly inhibits the rise in splanchnic glucose uptake induced by infusion of glucose; and (c) this effect does not require a fall in insulin and is modulated by the level of hyperglycemia. Our data indicate that the splanchnic bed is an important site of glucose uptake in postabsorptive humans and that epinephrine impairs glucose tolerance by suppressing glucose uptake by both splanchnic and peripheral tissues, as well as by its well known stimulatory effect on endogenous glucose production.

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Section: Discussioncontrasting

confidence: 43%

Mechanisms of Epinephrine-induced Glucose Intolerance in Normal Humans

Saccà¹,

Vigorito²,

Cicala³

et al. 1982

J. Clin. Invest.

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“…Furthermore, from another study where four patients without liver disease had a portal venous catheter inserted peroperatively (Holst et al, 1977), samples in an artery and the portal vein were taken after a single i.v. injection of 1 ml of 50% galactose per kg body weight ( Figs.…”

Section: Methodsmentioning

confidence: 99%

Splanchnic galactose uptake in patients with cirrhosis following single injection

Ranek

Lindskov

Tygstrup

et al. 1983

Clinical Physiology

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The galactose elimination capacity is used as a quantitative liver function test and is supposed to express the functioning liver cell mass. Clinical observations indicate, however, that the galactose elimination capacity overestimates functioning liver cell mass, and we therefore compare hepatic (splanchnic) and extrahepatic, extrarenal galactose elimination after a single injection of galactose in 23 patients with reduced liver function. The galactose elimination capacity was consistently greater than the hepatic (splanchnic) galactose elimination rate, estimated during liver vein catheterization. The difference was on the average 0.68 mmol min-1 (SD +/- 0.19, P less than 0.001) or about 40% of the galactose elimination capacity. If this difference, partly or fully, is due to extrahepatic extrarenal elimination, the clinical test for galactose elimination needs a correction (of the order of magnitude of 0.7 mmol min-1) to serve as an absolute measure of the hepatic functional capacity, but since the hepatic uptake rate may be underestimated following a single injection, the correction may be smaller.

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“…In a review of this subject in 1978, Unger stated: "...studies of the actions of exogenous glucagon on fuel homeostasis can be regarded as valid only if compensatory insulin secretion has been effectively blocked..." [1]. Changes in portal venous insulin concentrations likely account for previous failures to detect an effect of glucagon on postprandial carbohydrate tolerance in non-diabetic volunteers ' [7][8][9]. In the present experiment we studied C-peptide deficient individuals, thereby enabling us to control for insulin as a potential confounding variable.…”

Section: Discussionmentioning

confidence: 99%

“…Infusion of glucagon has been reported not to alter either intravenous or oral glucose tolerance in non-diabetic subjects [7][8][9]. While acute increases in glucagon can increase glucose [3][4][5], fasting glucagon concentrations in subjects with IDDM are only slightly higher than those present in non-diabetic subjects and increase minimally if at all following carbohydrate ingestion [1,2,10,11].…”

mentioning

confidence: 99%

Failure of glucagon suppression contributes to postprandial hyperglycaemia in IDDM

et al. 1995

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SummaryCarbohydrate ingestion results in a fall in glucagon concentration in non-diabetic but not in diabetic individuals. To determine if, and the mechanism by which, lack of postprandial suppression of glucagon contributes to hyperglycaemia, nine subjects with insulin-dependent diabetes mellitus (IDDM) ingested 50 g of glucose containing both [2-3HI glucose and [6-3H] glucose on two occasions. [6-14C] glucose, insulin and low-dose somatostatin were infused intravenously at the same rates on both occasions. A basal glucagon infusion was started either at the same time ("constant glucagon") or 2 h following ("suppressed glucagon") glucose ingestion. This resulted in lower (p < 0.001) glucagon concentrations during the first 2 h of the suppressed than during the constant glucagon study days (63 + 1 vs 108 + 2 pg/ ml). Lack of suppression of glucagon led to higher (p < 0.01) postprandial glucose concentrations (10.3+0.9 vs 8.1+0.7mmol/1) and a greater (p < 0.02) integrated glycaemic response. The excessive rise in glucose was due to higher (p < 0.02) rates of postprandial hepatic glucose release during the constant than during the suppressed glucagon study days, whether measured using either [6-3H] glucose (2.6 + 0.2 vs 2.0 + 0.2 mmol-kg -1 per 6 h) or [2-3H] glucose (3.0 + 0.3 vs 2.4 + 0.2 mmol-kg -1 per 6 h) as the meal tracer. Glucose disappearance, initial splanchnic glucose clearance and hepatic glucose cycling did not differ on the two occasions. Thus, the present studies demonstrate that lack of postprandial suppression of glucagon, by increasing hepatic glucose release, contributes to hyperglycaemia in subjects with IDDM. [Diabetologia (1995) 38: 337-343]

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The effect of intraportal and peripheral infusions of glucagon on insulin and glucose concentrations and glucose tolerance in normal man

Cited by 23 publications

References 16 publications

Mechanisms of Epinephrine-induced Glucose Intolerance in Normal Humans

Mechanisms of Epinephrine-induced Glucose Intolerance in Normal Humans

Splanchnic galactose uptake in patients with cirrhosis following single injection

Failure of glucagon suppression contributes to postprandial hyperglycaemia in IDDM

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