Physiological Effect of Glucagon in Human Isolated Adipocytes

Perea, A.; Clemente, Felipe; Martinell, J.; Villanueva-Peñacarrillo, María Luisa; Valverde, Isabel

doi:10.1055/s-2007-979981

Cited by 72 publications

(63 citation statements)

References 4 publications

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“…A physiologic role of glucagon per se in maintaining FFA levels is controversial. Several groups have reported a glucagon effect to increase lipolysis (18)(19)(20), whereas other studies have failed to observe any effect (21,22). Thus, while the fall in FFA observed in this study during low-dose insulin infusion may have been due to suppression of glucagon, there are several other possibilities.…”

Section: Discussioncontrasting

confidence: 54%

Causal linkage between insulin suppression of lipolysis and suppression of liver glucose output in dogs.

Rebrin¹,

Steil²,

Mittelman³

et al. 1996

J. Clin. Invest.

270

186

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Suppression of hepatic glucose output (HGO) has been shown to be primarily mediated by peripheral rather than portal insulin concentrations; however, the mechanism by which peripheral insulin suppresses HGO has not yet been determined. Previous findings by our group indicated a strong correlation between free fatty acids (FFA) and HGO, suggesting that insulin suppression of HGO is mediated via suppression of lipolysis. To directly test the hypothesis that insulin suppression of HGO is causally linked to the suppression of adipose tissue lipolysis, we performed euglycemic-hyperinsulinemic glucose clamps in conscious dogs ( n ϭ 8) in which FFA were either allowed to fall or were prevented from falling with Liposyn plus heparin infusion (LI; 0.

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Section: Discussioncontrasting

confidence: 54%

Causal linkage between insulin suppression of lipolysis and suppression of liver glucose output in dogs.

Rebrin¹,

Steil²,

Mittelman³

et al. 1996

J. Clin. Invest.

270

186

View full text Add to dashboard Cite

show abstract

“…Glucagon is stable across lactation in cattle, rats and sheep (Burnol et al, 1983;Sartin et al, 1985;Vernon and Pond, 1997). Glucagon stimulates both gluconeogenesis and lipolysis (Perea et al, 1995). Low levels of glucagon are puzzling in light of high levels of lipolysis and gluconeogenesis but probably contribute to protein sparing.…”

Section: Basal Glucose and Hormone Levelsmentioning

confidence: 99%

Hormonal regulation of glucose clearance in lactating northern elephant seals (Mirounga angustirostris)

Fowler

Champagne

Houser

et al. 2008

Journal of Experimental Biology

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SUMMARYNorthern elephant seals exhibit the rare strategy of fasting and lactating concomitantly. We investigated hormonal regulation of glucose clearance in northern elephant seals using glucose tolerance tests (GTT) performed early in lactation and again just prior to weaning. For comparison, identical measurements were made on separate females late in the molt fast. Serial blood samples were used to assess glucose clearance and hormone responses for 3 h post glucose injection. Plasma glucose remained elevated at the end of the sampling period in all groups. Glucose clearance rates were not significantly different among test groups. A significant insulin response was observed in early lactation, no significant response was observed late in lactation and an intermediate response was observed late in the molt fast. The insulin response to a glucose load decreased with adipose tissue proportions. Plasma glucagon decreased significantly following GTT in early and late lactation, although the magnitude of the depression was small in comparison to other species. Hypoinsulemia may be critical to facilitate net lipolysis late in lactation. Consistently low glucose clearance among test groups suggests insulin insensitivity within peripheral tissues. Glucagon suppression independent of insulin release suggests modification of the typical insulin-glucagon counter-regulation. These findings suggest that metabolic features of diabetic-like conditions may be adaptive in the context of long-term fasting.

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“…In adipocytes glucagon stimulates lipolysis, whereas in hepatocytes glucagon inhibits glycolysis, triacylglycerol synthesis, and stimulates gluconeogenesis, glycogenolysis, ketogenesis and beta oxidation of NEFA [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Glucagon increases circulating fibroblast growth factor 21 independently of endogenous insulin levels: a novel mechanism of glucagon-stimulated lipolysis?

et al. 2012

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Aims/hypothesis Glucagon reduces body weight by modifying food intake, glucose/lipid metabolism and energy expenditure. All these physiological processes are also controlled by fibroblast growth factor 21 (FGF-21), a circulating hepatokine that improves the metabolic profile in obesity and type 2 diabetes. Animal experiments have suggested a possible interaction between glucagon and FGF-21 however, the metabolic consequences of this crosstalk are not understood. Methods The effects of exogenous glucagon on plasma FGF-21 levels and lipolysis were evaluated in healthy volunteers and humans with type 1 diabetes, as well as in rodents with streptozotocin (STZ)-induced insulinopenic diabetes. In vitro, the role of glucagon on FGF-21 secretion and lipolysis was studied using isolated primary rat hepatocytes and adipocytes. Fgf-21 expression in differentiated rat pre-adipocytes was suppressed by small interfering RNA and released FGF-21 was immunoneutralised by polyclonal antibodies. Results Glucagon induced lipolysis in healthy human volunteers, patients with type 1 diabetes, mice and rats with STZ-induced insulinopenic diabetes, and in adipocytes isolated from diabetic and non-diabetic animals. In addition, glucagon increased circulating FGF-21 in healthy humans and rodents, as well as in patients with type 1 diabetes, and insulinopenic rodents. Glucagon stimulated FGF-21 secretion from isolated primary hepatocytes and adipocytes derived from animals with insulinopenic diabetes. Furthermore, FGF-21 stimulated lipolysis in primary adipocytes isolated from non-diabetic and diabetic rats. Reduction of Fgf-21 expression (by approximately 66%) or immunoneutralisation of released FGF-21 markedly attenuated glucagon-stimulated lipolysis in adipocytes. Conclusions/interpretation These results indicate that glucagon increases circulating FGF-21 independently of endogenous insulin levels. FGF-21 participates in glucagon-induced stimulation of lipolysis.

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Physiological Effect of Glucagon in Human Isolated Adipocytes

Cited by 72 publications

References 4 publications

Causal linkage between insulin suppression of lipolysis and suppression of liver glucose output in dogs.

Causal linkage between insulin suppression of lipolysis and suppression of liver glucose output in dogs.

Hormonal regulation of glucose clearance in lactating northern elephant seals (Mirounga angustirostris)

Glucagon increases circulating fibroblast growth factor 21 independently of endogenous insulin levels: a novel mechanism of glucagon-stimulated lipolysis?

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