The Role of the Liver in Glucagon Metabolism

Jaspan, Jonathan B.; Huen, A H; Morley, Colin G.D.; Moossa, A. R.; Rubenstein, A. H.

doi:10.1172/jci108791

Cited by 52 publications

(21 citation statements)

References 21 publications

(29 reference statements)

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“…Furthermore, little data are available on the hepatic clearance of glucagon in normal rats (41) and none in VMH-lesioned animals. Our perfusion data are compatible with what may happen in the portal vein in vivo.…”

Section: Resultsmentioning

confidence: 99%

Consequences of Ventromedial Hypothalamic Lesions upon Insulin and Glucagon Secretion by Subsequently Isolated Perfused Pancreases in the Rat

Rohner‐Jeanrenaud¹,

Jeanrenaud²

1980

J. Clin. Invest.

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A B S T R A C T The existence of a relationship between the ventromedial hypothalamic area (VMH) and the activity of the endocrine pancreas has been shown previously. This relationship has been further tested and extended in the present study, using isolated perfused pancreases from rats previously lesioned (4-7 d) in the VMH. It was found that in isolated pancreases obtained from rats fed ad lib. for 4 d after VMH lesions (i.e., that were hyperphagic), the typical biphasic pattern of insulin secretion was observed following glucose stimulation (20 mM) and that the total insulin output was much greater than that of controls. The increased insulin output was not a result of hyperphagia because similar results were obtained using pancreases obtained from VMH-lesioned rats in which a food restriction matching exactly that ofcontrol rats was started either immediately or 3 d after the lesions. Pancreases from such food-restricted VMHlesioned rats oversecreted insulin, when compared with controls fed the same amount, from 7 mM of glucose concentration in perfusion medium onwards. After the addition of arginine (10 mM), the total output of glucagon by pancreases from food-restricted VMHlesioned rats was twice that of controls. Qualitatively, the arginine-induced glucagon secretion by pancreases from food-restricted VMH-lesioned rats retained its biphasic pattern. Similarly, epinephrine (0.1 ,uM) elicited a greater glucagon release by pancreases from food-restricted VMH-lesioned rats when compared with controls. These data further support the concept of a link (as yet undefined) between the hypothalamus and the endocrine pancreas, as lesions of the VMH area resulted in abnormal secretion not only of insulin, but of glucagon as well.

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Section: Resultsmentioning

confidence: 99%

Consequences of Ventromedial Hypothalamic Lesions upon Insulin and Glucagon Secretion by Subsequently Isolated Perfused Pancreases in the Rat

Rohner‐Jeanrenaud¹,

Jeanrenaud²

1980

J. Clin. Invest.

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“…Under transient conditions, 2 min after glucagon injection, the dependence of the increase in glucose 6-phosphate on hormone concentration was studied. With 0.2nmol glucagon/l, which can be regarded as a physiological concentration in the portal vein [20,211, the content of glucose 6-phosphate was doubled; it was more than tripled with 15 nmol/l (Fig. 2).…”

Section: Distribution Of Glucose and Glucose 6-phosphatementioning

confidence: 96%

“…Assuming an extracellular space of 30 ml/l50 g body weight [19] injection of 150 pg, 1.5 pg and 25 ng glucagon (molecular weight 3500) yielded an extracellular hormone concentration of 1.5 pmol/l, 15 nmol/l and 0.2 nmol/l, resp. With the calculation of the latter value a basal glucagon concentration of 0.05 nmol/l was taken into consideration [20,211.…”

Section: Glucagon Treatmentmentioning

confidence: 99%

The Glucose/Glucose‐6‐Phosphate Cycle in the Periportal and Perivenous Zone of Rat Liver

Jungermann¹,

Heilbronn²,

Katz³

et al. 1982

European Journal of Biochemistry

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Periportal and perivenous hepatocytes contain different activities ( V ) of antagonistic key enzymes such as glucokinase and glucose-6-phosphatase. In order to get an insight into the metabolism of the periportal and perivenous area the flux rates (v) of the glucose/glucose-6-phosphate cycle were calculated on the basis of the Michaelis-Menten equation using the measured zonal concentrations of glucose and glucose 6-phosphate, the zonal activities of glucokinase and glucose-6-phosphatase previously reported and the half-saturating substrate concentrations (K,) of the two enzymes found in the literature. The concentrations of glucose were obtained as a first approximation by measuring the concentrations in portal (= periportal) and hepatovenous (= perivenous) blood; those of glucose 6-phosphate were calculated from the levels determined in microdissected periportal and perivenous liver tissue.The calculations showed (a) that the overall cycling rates agreed remarkably well with those reported for intact animals and (b) that during a normal feeding rhythm the periportal zone should catalyze net glucose output and the perivenous zone should mediate net glucose uptake, as proposed by the model of 'metabolic zonation'.Hepatocytes from the periportal (afferent) and perivenous (efferent) zone of the liver parenchyma differ in their enzyme equipments and subcellular structures [I, 21. This heterogeneity led to the model of 'metabolic zonation' [3,4]. It was proposed that the periportal hepatocytes, which are rich in glucose-6-phosphatase [5, 61, fructose-I ,6-bisphosphatase [7. 81 and phosphornolpyruvate carboxykinase [9], predominantly catalyze glucogenesis and that the perivenous cells, which are rich in glucokinase [7, 101 and pyruvate kinase [9], mainly mediate glycolysis.In the present investigation the cytosolic concentrations of glucose and of glucose-6-phosphate were measured in order to calculate the flux rates of the glucose/glucose-6-phosphate cycle in the periportal and perivenous zone of rat liver under different physiological conditions. The flux rates were to be determined using the measured zonal concentrations of glucose and glucose 6-phosphate, the zonal activities of glucokinase and glucose-6-phosphatase, as reported previously [5, 71, and the half-saturating substrate concentrations, as known from the literature [I 1 -151.It was found that the glucose concentrations in the periportal and perivenous zone were the same or formed a slight gradient depending on the metabolic situation, while the glucose-6-phosphate concentrations in the two zones were not significantly different under various conditions. Calculation of the flux rates revealed that normally the periportal zone

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“…Recent studies have pointed out that plasma glucagon immunoreactivity is heterogeneous (Valverde et al, 1970;Valverde et al, 1974;Weir et al, 1975;Valverde and Villanueva, 1976;Kuku et al, 1976;Jaspan et al, 1977) and has as many as four fractions when determined with antiserum 30K. There is at present little information regarding the immunoreactive nature of Big Plasma Glucagon (BPG) (Valverde et al, 1974) and 2000 mol.…”

Section: Endocrinolmentioning

confidence: 99%

“…Jaspan et al (1977) showed that the liver was the major metabolic site of the 3500 molecular weight glucagon.…”

mentioning

confidence: 99%

Size heterogeneity of immunoreactive glucagon during bile-duct obstruction in the rabbit.

Sanke

1982

Endocrinol Japon

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The influences of bile-duct obstruction upon basal plasma glucagon levels and the relationships between glucagon-like substance in bile and postobstructive plasma glucagon were examined in the rabbit.Immunoreactive glucagon (IRG) was measured with antiserum 30 K (Unger).Bile-duct obstruction was followed by a prompt rise within 60 minutes in plasma IRG which was four times the basal value, but had little influence on plasma immunoreactive insulin and blood sugar.The biliary IRG and the elevated plasma IRG during bile-duct obstruction were filtrated with a Bio-Gel P-10 column. Most of the postobstructive plasma IRG appeared in the void volume area (plasma large IRG), while almost all of the biliary IRG was recovered in the position equivalent to approximately 2000 daltons (biliary IRG 2000). Both IRGs of different molecular sizes revealed similar dilution curves in radioimmunoassay to that with porcine glucagon. After incubation of bile with preobstructive plasma, the IRG elution profile of the mixture contained an increased amount of large molecular size IRG similar to that of postobstructive plasma in regard to 30K specificity and elution position.The disappearance of IRG in the void volume area was observed when the bile-plasma mixture or the postobstructive plasma was filtrated with acidic buffer.These results suggest that plasma large IRG contributing to hyperglucagonemia during bile-duct obstruction may be derived from biliary IRG 2000.

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The Role of the Liver in Glucagon Metabolism

Cited by 52 publications

References 21 publications

Consequences of Ventromedial Hypothalamic Lesions upon Insulin and Glucagon Secretion by Subsequently Isolated Perfused Pancreases in the Rat

Consequences of Ventromedial Hypothalamic Lesions upon Insulin and Glucagon Secretion by Subsequently Isolated Perfused Pancreases in the Rat

The Glucose/Glucose‐6‐Phosphate Cycle in the Periportal and Perivenous Zone of Rat Liver

Size heterogeneity of immunoreactive glucagon during bile-duct obstruction in the rabbit.

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