Hyperglucagonemia in Laennec's Cirrhosis

Sherwin, Robert S.; Joshi, Prakash; Hendler, Rosa; Felig, Philip; Conn, Harold O.

doi:10.1056/nejm197401312900502

Cited by 233 publications

(29 citation statements)

References 24 publications

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“…The peripheral hyperinsulinemia that has been described after portacaval shunt [3,14,15] was not consistently seen. However, increased glucagon levels in the systemic venous blood were regularly observed in confirmation of earlier reports [26,30,31], As might be expected with hyperglucagonemia in combination with a bypassing of insulin around the liver, the hepatic cyclic AMP was consistently elevated in the dogs, but, surprisingly, not in the baboons. The canine increases occurred in spite of the fact that cyclic AMP production as measured by the aminophylline test was not strikingly increased.…”

Section: Discussionsupporting

confidence: 87%

“…Alternatively, Eaton [16] has proposed that changes in glucagon metabolism might be important in causing the antilipidemic effect. Portacaval shunting has also been demonstrated to cause increases in serum glucagon concentration [26,30,31]. Glucagon in pharmacologic [27] or physiologic [37] doses has been shown to decrease hepatic cholesterol synthesis possibly via an increase in hepatic cyclic adenosine 3′,5′-monophosphate (cyclic AMP).…”

Section: Discussionmentioning

confidence: 99%

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The effect of portacaval shunt upon hepatic cholesterol synthesis and cyclic AMP in dogs and baboons

Francavilla

Jones

Benichou

et al. 1980

Journal of Surgical Research

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Hepatic cholesterol synthesis, hepatic cyclic AMP, and portal and peripheral insulin and glucagon levels were investigated in nine dogs and three baboons after complete portacaval shunt. Cholesterol synthesis as measured with acetate incorporation was reduced in both species. Hepatic cyclic AMP increased in dogs. Changes in portal and systemic insulin were inconsistent, but hyper-glucagonemia occurred regularly. Diminished hepatic cholesterol synthesis is apparently one factor, although probably not the only one, in the antilipidemic effect of portacaval shunt. This altered cholesterol metabolism may be due to a change in the hormonal environment of the liver caused by portal diversion.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

The effect of portacaval shunt upon hepatic cholesterol synthesis and cyclic AMP in dogs and baboons

Francavilla

Jones

Benichou

et al. 1980

Journal of Surgical Research

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“…Previous reports have indicated that 0.1-1.0 mM NH4+ inhibits glucose-stimulated insulin release both in vitro using pieces of pancreas removed from the golden hamster (11) and in vivo in rats (13) and men (12) infused with NH4+. A role for NH4+ in the abnormality of islet function seen in cirrhotic patients (12,31) was also documented.…”

Section: Methodsmentioning

confidence: 90%

The stimulus-secretion coupling of glucose-induced insulin release. Metabolic and functional effects of NH4+ in rat islets.

Sener¹,

Hutton²,

Kawazu³

et al. 1978

J. Clin. Invest.

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A B S T R AC T NH4+ caused a dose-related, rapid, and reversible inhibition of glucose-stimulated insulin release by isolated rat islets. It also inhibited glyceraldehyde-, Ba2+-, and sulfonylurea-stimulated insulin secretion. NH4 failed to affect glucose utilization and oxidation, glucose-stimulated proinsulin biosynthesis, the concentration of ATP, ADP, and AMP, and the intracellular pH. NH4+ also failed to affect the ability oftheophylline and cytochalasin B to augment glucoseinduced insulin release. However, in the presence and absence of glucose, accumulation of NH4+ in islet cells was associated with a fall in the concentration ofNADH and NADPH and a concomitant alteration of "Rb+ and 45Ca2+ (or 133Ba2+) handling. These findings suggest that reduced pyridine nucleotides, generated by the metabolism of endogenous or exogenous nutrients, may modulate ionophoretic processes in the islet cells and by doing so, affect the net uptake of Ca2+ and subsequent release of insulin.

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“…Cirrhosis is characterized by a number of abnormalities in circulating substrate and hormone concentrations including FFA (13)(14)(15), glucagon (54), growth hormone (55), norepinephrine (56), and insulin itself(l-8). Moreover, an increase in each of these substrates has been shown to be associated with the development of insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

Effect of physiologic hyperinsulinemia on glucose and lipid metabolism in cirrhosis.

Petrides¹,

Groop²,

Riely³

et al. 1991

J. Clin. Invest.

138

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Insulin secretion and insulin sensitivity were evaluated in eight clinically stable cirrhotic patients and in 12 controls. OGTT was normal in cirrhotics but plasma insulin response was increased approximately twofold compared with controls. Subjects received a three-step (0.1, 0.5, 1.0 mU/kg -min) euglycemic insulin clamp with indirect calorimetry, 16-311J-glucose, and 11-"CJ-palmitate. During the two highest insulin infusion steps glucose uptake was impaired (333±031 vs. 5.06±0.40 mg/ kg. min, P < 0.01, and 6.09+0.50 vs. 7.95±0.52 mg/kg.m-, P < 0.01). Stimulation of glucose oxidation by insulin was normal; in contrast, nonoxidative glucose disposal (i.e., glycogen synthesis) was markedly reduced. Fasting (r = -0.553, P < 0.01) and glucose-stimulated (r = -0.592, P < 0.01) plasma insulin concentration correlated inversely with the severity of insulin resistance. Basal hepatic glucose production was normal in cirrhotics and suppressed normally with insulin. In postabsorptive state, plasma FFA conc (933±42 vs. 711±44 Mmol/ liter, P < 0.01) and FFA turnover (9.08±1.20 vs. 6. 03±0.53 ,umol/kg min, P < 0.01) were elevated in cirrhotics despite basal hyperinsulinemia; basal FFA oxidation was similar in cirrhotic and control subjects. With low-dose insulin infusion, plasma FFA oxidation and turnover failed to suppress normally in cirrhotics. During the two higher insulin infusion steps, all parameters of FFA metabolism suppressed normally. In summary, stable cirrhotic patients with normal glucose tolerance exhibit marked insulin resistance secondary to the impaired nonoxidative glucose disposal. Our results suggest that chronic hyperinsulinism may be responsible for the insulin resistance observed in cirrhosis. (J. Clin. Invest. 1991. 88:561-570.)

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Hyperglucagonemia in Laennec's Cirrhosis

Cited by 233 publications

References 24 publications

The effect of portacaval shunt upon hepatic cholesterol synthesis and cyclic AMP in dogs and baboons

The effect of portacaval shunt upon hepatic cholesterol synthesis and cyclic AMP in dogs and baboons

The stimulus-secretion coupling of glucose-induced insulin release. Metabolic and functional effects of NH4+ in rat islets.

Effect of physiologic hyperinsulinemia on glucose and lipid metabolism in cirrhosis.

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