Decreased feeding in rats following hepatic-portal infusion of glucagon

Martin, James R.; Novin, Donald

doi:10.1016/0031-9384(77)90218-9

Cited by 112 publications

(19 citation statements)

References 22 publications

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“…With the supraphysiologic dose of glucagon used, five of the experimental animals showed diminished food consumption and, consequently, low weight gain when compared to controls. Glucagon may exert a direct effect on appetite by functioning as a satiety signal (23)(24)(25) or by inhibition of gastrointestinal motility (26)(27)(28). The hypothesis that the former effect is mediated through the level of glycemia (25) is not supported by either the present study or our previously published data (9).…”

Section: Discussioncontrasting

confidence: 66%

Preserved Fetal Plasma Amino Acid Concentrations in the Presence of Maternal Hypoaminoacidemia

et al. 1986

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ABSTRACT. The effects on the conceptus of persistently decreased maternal plasma amino acid concentrations were studied in pregnant rats by the infusion of glucagon (0.21 mglday) to the mother from day 14 to 20 of gestation with a subcutaneous, osmotically driven minipump. Controls received diluent. The experimental animals either had normal caloric intake and weight gain, or diminished caloric intake with no weight gain. Both experimental groups exhibited a decrease in plasma total amino acid concentration of approximately 50%. Maternal plasma glucose and insulin concentrations were unaffected except for slight decreases in the low weight gain group. At cesarean section on day 20, fetal weight was unaffected in the normal weight gain group, while the low weight gain animals exhibited intrauterine growth retardation. Fetal plasma glucose and insulin concentrations were unaffected. Despite the marked decrease in maternal plasma total amino acid concentration, fetal plasma total amino acid concentration was unaffected. Individual plasma amino acid concentrations in the normal weight gain mothers and fetuses revealed a spectrum of changes. Some maternal amino acids were decreased by more than 60% (a-aminobutyric acid, asparagine, threonine, glutamine, alanine) while others were unaffected (tyrosine, tryptophan, phenylalanine, histidine). In general, amino acids that were decreased in the mother exhibited no change or a lesser decrease in fetal plasma concentration, while those that were unaffected in the mothers showed increased fetal concentrations. Fetuses from the low weight gain mothers had plasma amino acid ~rofiles that were similar to those of the normal weight gain mothers. We speculate that the preserved fetal amino acid concentrations are due to enhanced placental transport of amino acid secondary to maternal substrate decrease. (Pediatr Res 20: 1071-1076,1986 which are specific for each group of nutrients. In the case of amino acids it has been demonstrated that the placenta is capable of concentrating most amino acids intracellularly in order to achieve transport to the fetus against a concentration gradient (1-4). This results in fetal plasma amino acid concentrations which can be more than three times higher than maternal plasma concentrations (1, 5 , 6).Maternal substrate limitation, presumably by limiting nutrient transport to the fetus, can lead to IUGR. This has been demonstrated experimentally in models utilizing starvation (7) or ligation of the uterine artery (8). These manipulations result in nonspecific reduction in the delivery of substrates, including glucose and amino acids, such that the roles of specific substrates remain obscure.The aim of the present study was to develop a model in which maternal plasma amino acid concentrations are selectively reduced without significant changes in the maternal concentrations of other nutrients. In nonpregnant male rats, a persistent increase in glucagon has been shown to be associated with a decrease in total plasma amino acid concentrations (9). Thi...

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Section: Discussioncontrasting

confidence: 66%

Preserved Fetal Plasma Amino Acid Concentrations in the Presence of Maternal Hypoaminoacidemia

et al. 1986

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“…However, results obtained in the present study from direct infusions of isotonic glucose into the HPV suggest that absorbed glucose is indeed a factor in regulating food intake, and that the liver is involved. Studies by VanderWeele et al (1976), Martin and Novin (1977) and Novin and VanderWeele (1977) with mammals suggest that, from results of HPV glucose infusions, glucostatic regulation of intake is dependent on the concentration of liver glycogen and its metabolism via glycogenolysis, possibly dependent in turn on the action of glucagon.…”

Section: Discussionmentioning

confidence: 96%

Evidence for hepatic glucostatic regulation of food intake in the domestic chicken and its interaction with gastro‐intestinal control

Shurlock

Forbes

1981

British Poultry Science

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1. Male birds of a laying strain had permanent catheters introduced into the hepatic portal vein via the coccygeo-mesenteric vein. 2. Infusions of 5 ml of 40, 100 or 150 g glucose/l solution over 2 min caused a non-significant depression of food intake compared with a 9 g NaCl/l control solution. 3. Infusions of a range of isotonic glucose solution (0 to 60 g glucose/l, 30- mosm) at 1.4 ml/min over 3 h caused food intake depression within the 3-h period (P less than 0.01) proportional to the logarithm of the dose. 4. This effect was not observed when 60 g glucose/l was infused at the above rates into the jugular vein. 5. Starvation of the bird for 21 h accentuated the depressive effect of glucose load on food intake, especially when birds were not given food until after the 3-h infusion. 6. The infusion of solutions of sodium chloride (1.0 to 13.0 g/l, 33 to 433 mosmoles/kg) at 1.4 ml/min over 3 h stimulated food intake within the range of 3 to 7 g NaCl/l (100 to 233 mosm) but suppressed intake outside this range. This can be interpreted as a possible interaction with water intake control. 7. Infusion of 20 ml of glucose solution (0, 18 or 54 g/l) over 5 min into the crop and 0, 3.75 or 60 g glucose/l at 1.4 ml/min over 3 h into the hepatic portal vein, caused an additive, linear depression of food intake.

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“…Under conditions of hypoglycemia, glucagon elevates blood glucose by promoting glycogenolysis and gluconeogenesis, as well as hepatic fatty acid β-oxidation and ketogenesis (MacDonald et al, 2007; Cryer, 2012). Peripheral administration of glucagon decreases food intake in rats and humans (Penick and Hinkle, 1961; Martin and Novin, 1977). Moreover, glucagon infusion increases oxygen consumption in rats and increases resting energy expenditure in humans (Davidson et al, 1957; Nair, 1987).…”

Section: Pharmacotherapies For Obesitymentioning

confidence: 99%

Obesity: Current and potential pharmacotherapeutics and targets

Narayanaswami

Dwoskin

2017

Pharmacology & Therapeutics

155

121

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Obesity is a global epidemic that contributes to a number of health complications including cardiovascular disease, type 2 diabetes, cancer and neuropsychiatric disorders. Pharmacotherapeutic strategies to treat obesity are urgently needed. Research over the past two decades has increased substantially our knowledge of central and peripheral mechanisms underlying homeostatic energy balance. Homeostatic mechanisms involve multiple components including neuronal circuits, some originating in hypothalamus and brain stem, as well as peripherally-derived satiety, hunger and adiposity signals that modulate neural activity and regulate eating behavior. Dysregulation of one or more of these homeostatic components results in obesity. Coincident with obesity, reward mechanisms that regulate hedonic aspects of food intake override the homeostatic regulation of eating. In addition to functional interactions between homeostatic and reward systems in the regulation of food intake, homeostatic signals have the ability to alter vulnerability to drug abuse. Regarding the treatment of obesity, pharmacological monotherapies primarily focus on a single protein target. FDA-approved monotherapy options include phentermine (Adipex-P®), orlistat (Xenical®), lorcaserin (Belviq®) and liraglutide (Saxenda®). However, monotherapies have limited efficacy, in part due to the recruitment of alternate and counter-regulatory pathways. Consequently, a multi-target approach may provide greater benefit. Recently, two combination products have been approved by the FDA to treat obesity, including phentermine/topiramate (Qsymia®) and naltrexone/bupropion (Contrave®). The current review provides an overview of homeostatic and reward mechanisms that regulate energy balance, potential therapeutic targets for obesity and current treatment options, including some candidate therapeutics in clinical development. Finally, challenges in anti-obesity drug development are discussed.

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Decreased feeding in rats following hepatic-portal infusion of glucagon

Cited by 112 publications

References 22 publications

Preserved Fetal Plasma Amino Acid Concentrations in the Presence of Maternal Hypoaminoacidemia

Preserved Fetal Plasma Amino Acid Concentrations in the Presence of Maternal Hypoaminoacidemia

Evidence for hepatic glucostatic regulation of food intake in the domestic chicken and its interaction with gastro‐intestinal control

Obesity: Current and potential pharmacotherapeutics and targets

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