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To determine whether volatile fatty acids (VFA) are involved in the regulation of plasma concentrations of insulin or glucagon in the goat, VFA, separately or in combination, were administered into the jugular vein, the portal vein or the rumen, and their effects on pancreatic hormones as well as on VFA measured in venous blood. Propionate, n-butyrate and n-valerate, but not acetate, injected in pharmacological doses, were potent stimuli not only of the secretion into the plasma of insulin but also of glucagon. As regards insulin, the response to VFA was probably not mediated to an appreciable extent by glucose or glucagon. β-Hydroxybutyrate did not mediate the effect of n-butyrate on insulin and glucagon. The effects of VFA appear to be peculiar to the ruminant since in the rat injection of similar doses resulted in either no changes or very small changes of plasma insulin and glucagon.
Intraportal infusions over 4 h of mixtures of VFA, resulting in less extreme, more physiological blood concentrations of VFA, elicited sudden transient increases in insulin and to a lesser extent in glucagon. After these peaks insulin and glucagon declined to preinfusion levels and remained virtually unaltered during the remainder of the infusion in spite of sustained, raised concentrations of VFA in the peripheral circulation. These results suggest that under these conditions the rate of increase of VFA is a signal for the secretion of pancreatic hormones. Intraruminal infusions, representing a more physiological route of administration, of single VFA at high rates resulted in a small increase in insulin for propionate infusion only, whereas a mixture of VFA at a physiological rate induced barely any change in insulin or glucagon. It is concluded that under physiological conditions the rate of increase of VFA may contribute to the insulin secretion in the free-feeding goat, but it is unlikely that VFA are the sole controlling agents of insulin release. It is even less probable that the release of glucagon is governed by VFA in the free-feeding goat.
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Glucagon and insulin receptors were examined in relation to plasma concentrations of hormones and metabolites in unmated and in 110- and 140-day pregnant ewes (four animals per group). The concentrations of insulin, growth hormone and non-esterified fatty acids in the circulation, together with the maintenance of body weight, suggested that the animals were in energy surplus. When compared with the unmated group the binding of insulin to isolated hepatocytes increased by 110 days of pregnancy, attaining statistical significance (P < 0·02) after 140 days. Conversely, glucagon binding was reduced by 110 days of pregnancy, also attaining statistical significance (P < 0·02) after 140 days.
The changes in both insulin and glucagon binding were primarily due to changes in the number of receptors on each hepatocyte, although some fluctuations in receptor affinity were also found.
These observations suggested that the number of hepatic insulin and glucagon receptors are altered during the metabolic demands of pregnancy in sheep, but unlike the changes reported during lactation in the ewe and restricted energy intake in the goat, they are not related either to energy deficit or to changes in the concentration of insulin, and probably of glucagon, in the circulation.
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Third Division, Department of Medicine, University of Kobe, Kobe, Japan
(Received 21 November 1975)
It has been shown that glucagon secretion from the perfused rat pancreas is enhanced by arginine (Assan, Boillot, Attali, Soufflet & Ballerio, 1972) and suppressed by glucose (Gerich, Charles & Grodsky, 1974). However, the effect of fructose on glucagon secretion remains unclear, although fructose is known to potentiate glucose- and mannose-induced insulin secretion (Curry, Curry & Gometz, 1972; Curry, 1974). The present study investigated the effect of fructose on arginine-induced glucagon and insulin release in perfused rat pancreas.
The perfusion of isolated rat pancreas was performed by the procedure described by Grodsky, Batts, Bennett, Vcella, McWilliams & Smith (1963) with minor modifications. The splenic vessels were ligatured at the hilum, and the left gastric vessels were also ligatured. Perfusate (3·8% dextran and 0·25% bovine serum albumin in Krebs-Ringer-bicarbonate buffer) containing 2·8 mm-glucose (Expt 1),
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Liver cirrhosis is often accompanied by a disturbed carbohydrate metabolism similar to type 2 diabetes. To investigate the severity of the defect in insulin secretion in this form of diabetes, we measured insulin release from isolated pancreatic islets of rats with CCl(4)-phenobarbital-induced liver cirrhosis. Cirrhosis was confirmed by clinical signs, elevated liver enzymes and histology. Fasting venous plasma glucose concentrations were equal in rats with liver cirrhosis and in controls. Plasma insulin and glucagon concentrations were significantly greater (P<0.01) in cirrhotic rats than in control animals. Glucose (16.7 mM)-induced stimulation of insulin release from pancreatic islets revealed a twofold increase in control and cirrhotic rats. Basal and stimulated insulin secretion, however, were significantly lower in cirrhotic animals. The incretin hormone, glucagon-like peptide-1 (GLP-1), has therapeutic potential for the treatment of type 2 diabetes. Therefore, islets from control and cirrhotic animals were incubated with GLP-1 in concentrations from 10(-)(11) to 10(-)(6) M. GLP-1 stimulated insulin release in a concentration-dependent manner. In islets from cirrhotic rats, basal and stimulated insulin secretion was blunted compared with controls. These data show that the hyperinsulinemia observed in liver cirrhosis is not due to an increase of insulin secretion from islets, but could be explained by decreased hepatic clearance of insulin. GLP-1 may ameliorate diabetes in patients with liver cirrhosis.
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ABSTRACT
The effects of plasma free fatty acids (FFA) and somatostatin-14 (S-14) on concentrations of plasma GH, glucagon and insulin were investigated in juvenile ducks. Oleic acid, S-14 or both were infused into 4- to 7-week-old birds and plasma GH, glucagon-like immunoreactivity (GLI), immunoreactive insulin (IRI) and FFA were measured.
An increase in plasma GH and a decrease in GLI but no change in IRI was observed after infusion of 9 mg oleic acid/kg per min. A decrease in plasma GH, FFA and IRI and an increase in plasma GLI was seen after infusion of 800 ng S–14/kg per min. These effects of S-14 on IRI and GLI were abolished when S-14 was infused simultaneously with oleic acid.
It is concluded that FFA have a direct stimulatory effect on GH secretion and an inhibitory effect on glucagon secretion. Somatostatin-14 directly inhibits the secretion of GH and its stimulatory effect on the secretion of glucagon is mediated by a depression in concentrations of plasma FFA. Finally, S-14 has no effect on plasma insulin when basal levels of plasma FFA are maintained.
J. Endocr. (1985) 106, 21–25
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SUMMARY
The level of plasma free fatty acids (FFA) in both laying and immature non-laying hens was not markedly decreased by intravenously injected amounts of glucose sufficient to double the level of plasma glucose for 15–30 min. This was true for fasting and for fed birds. Adrenocorticotrophic hormone (ACTH) given i.v. to laying birds produced a definite increase in the levels of plasma FFA and glucose in doses of 60 i.u./kg. Daily doses of long-acting ACTH given i.m. for 3 days to laying birds produced a marked increase in plasma glucose accompanied by a pronounced fall in plasma FFA. Insulin markedly lowered the plasma glucose level in both mature and immature birds and caused a large and immediate increase in plasma FFA. Glucagon also induced a marked increase in plasma FFA accompanied by a rise in plasma glucose. The effects of insulin and glucagon were not abolished by pretreating the birds with reserpine or hexamethonium bromide. It is concluded that the effect of glucagon on plasma FFA is probably a result of a direct action on avian adipose tissue and that insulin may promote a similar response by an increased release of glucagon from the pancreas.
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An antibody to porcine calcitonin (CT) was selected which cross-reacted completely to bovine CT in a radioimmunoassay using a synthetic porcine CT preparation (CT-s) labelled with 125I (Lequin, Hackeng, Schopman & Care, 1970). With this radioimmunoassay it has been possible to measure CT concentrations in samples of bovine peripheral and thyroid venous plasma. All concentrations of CT reported here are expressed in terms of immunologically active CT-s/ml. The standard error of the CT measurements was ± 50 pg CT-s/ml over the range of concentration 250–2000 pg/ml.
One lobe of the thyroid gland was isolated in situ in each of three calves (33–38 kg body wt) and in one adult Jersey cow (300 kg body wt). The glands were perfused with blood which contained various concentrations of calcium. Glucagon and the kallikrein inhibitor (KI) aprotinin (Zymofren) were also added in an experiment with the cow to give perfusing concentrations of
School of Biology and Biochemistry, Medical Biology Centre, Queen’s University of fBelfast, Lisburn Road, Belfast, Northern Ireland, UK
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School of Biology and Biochemistry, Medical Biology Centre, Queen’s University of fBelfast, Lisburn Road, Belfast, Northern Ireland, UK
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School of Biology and Biochemistry, Medical Biology Centre, Queen’s University of fBelfast, Lisburn Road, Belfast, Northern Ireland, UK
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School of Biology and Biochemistry, Medical Biology Centre, Queen’s University of fBelfast, Lisburn Road, Belfast, Northern Ireland, UK
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School of Biology and Biochemistry, Medical Biology Centre, Queen’s University of fBelfast, Lisburn Road, Belfast, Northern Ireland, UK
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School of Biology and Biochemistry, Medical Biology Centre, Queen’s University of fBelfast, Lisburn Road, Belfast, Northern Ireland, UK
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School of Biology and Biochemistry, Medical Biology Centre, Queen’s University of fBelfast, Lisburn Road, Belfast, Northern Ireland, UK
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School of Biology and Biochemistry, Medical Biology Centre, Queen’s University of fBelfast, Lisburn Road, Belfast, Northern Ireland, UK
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School of Biology and Biochemistry, Medical Biology Centre, Queen’s University of fBelfast, Lisburn Road, Belfast, Northern Ireland, UK
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Introduction Glucose-dependent insulinotrophic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are important gastrointestinal-releasing hormones involved in the regulation of postprandial nutrient homeostasis ( Meier et al
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Twelve patients with non-insulin dependent diabetes mellitus (NIDDM) under secondary failure to sulfonylureas were studied to evaluate the effects of subcutaneous glucagon-like peptide-1(7-36)amide (GLP-1) on (a) the gastric emptying pattern of a solid meal (250 kcal) and (b) the glycemic and endocrine responses to this solid meal and an oral glucose tolerance test (OGTT, 300 kcal). 0.5 nmol/kg of GLP-1 or placebo were subcutaneously injected 20 min after meal ingestion. GLP-1 modified the pattern of gastric emptying by prolonging the time to reach maximal emptying velocity (lag period) which was followed by an acceleration in the post-lag period. The maximal emptying velocity and the emptying half-time remained unaltered. With both meals, GLP-1 diminished the postprandial glucose peak, and reduced the glycemic response during the first two postprandial hours by 54.5% (solid meal) and 32.7% (OGTT) (P < 0.05). GLP-1 markedly stimulated insulin secretion with an effect lasting for 105 min (solid meal) or 150 min (OGTT). The postprandial increase of plasma glucagon was abolished by GLP-1. GLP-1 diminished the postprandial release of pancreatic polypeptide. The initial and transient delay of gastric emptying, the enhancement of postprandial insulin release, and the inhibition of postprandial glucagon release were independent determinants (P < 0.002) of the postprandial glucose response after subcutaneous GLP-1. An inhibition of efferent vagal activity may contribute to the inhibitory effect of GLP-1 on gastric emptying.
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Levels of endogenous somatostatin, gastric inhibitory polypeptide (GIP), glucagon and insulin were measured during gastric (abomasal) emptying in the conscious calf. Isotonic NaHCO3 infused into the duodenum increased rates of emptying of a saline test meal and of gastric acid secretion, but had no effect on basal levels of blood glucose, somatostatin, GIP, insulin or glucagon. By contrast, intraduodenal infusion of 60 mm-HCl caused complete inhibition of gastric emptying, reduction of acid secretion, and an immediate increase in plasma somatostatin from 121·3 ± 9·4 (s.e.m.) to 286·3 ± 16·3 pg/ml (P <0·01) but levels of GIP, insulin, glucagon and glucose were unaltered. Intravenous injection of somatostatin (0·5 μg/kg) suppressed the antral electromyographic recording and gastric efflux so long as plasma somatostatin levels remained above approx. 200 pg/ml. This suggests that somatostatin can be released by intraduodenal acidification and that it inhibits gastric function by an endocrine effect. Since somatostatin retards gastric emptying it may therefore have an indirect role in nutrient homeostasis by limiting discharge of gastric chyme to the duodenum.
