Über die radioimmunologische Bestimmung von Insulin im Blut

Melani, F; Ditschuneit, H.; Bartelt, K. M.; Friedrich, H.; Pfeiffer, E. F.

doi:10.1007/bf01747863

Cited by 188 publications

(63 citation statements)

References 13 publications

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“…It has been found previously [15,16] and conf~'med in the studies reported here, that diabetes mellitus is associated with hyperglucagonemia and an impaired suppression of alpha cell function by high glucose concentrations. This has been attributed mainly to the Iaek of insulin.…”

Section: Discussionsupporting

confidence: 67%

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Hyperglucagonemia of the isolated perfused pancreas of diabetic mice (db/db)

et al. 1973

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Summary. Diabetes mellitus is held to be accompanied by inappropriately high levels of plasma glueagon relative to blood glucose concentrations. This has been interpreted as indicating lack of insulin. To establish ghcagon release in presence of high levels of endogenous insulin, the effects of both glucose and arginine were studied in the isolated perfused pancreas of genetically diabetic mice (db/db). Stimulation with glucose 2.75 mM or glucose plus arginine 8.25 mM exhibited a pronounced hyperglueagonemia. Following glucose 8.25 raM, however, there was no depression of glucagon secretion. Despite excessive high levels of endogenous insulin, there was a pattern of rather non-suppressible glueagon release. Lack of insulin per se, therefore, is unlikely to be the sole cause of hyperglucagonemia in this type of genetic animal diabetes mellitus.Key words : Diabetic mice, isolated perfused pancreas, high insulin levels, hyperglucagonemia.Patients with inherited diabetes mellitus are said to demonstrate increased pancreatic glueagon release relative to blood sugar levels [25,16]. Extremely high levels of glueagon have also been reported in alloxan treated dogs [17], streptozotoein diabetic rats [13] and in patients with severe ketoacidosis [1]. This has been interpreted as a state of decreased suppressibility of the alpha cell in the diabetics, probably on the base of lack of insulin. Infusion of insulin in animals with artificially achieved diabetes corrected instantly the state of hyperglucagonemia.Recent studies-in diabetic patients, however, exhibited only a slow and modest decline of glueagon after infusion of high insulin dosages. It was, therefore, concluded that mere lack of insulin may not adequately explain the alpha cell abnormality in diabetes mellitus [26]. Most of these patients, however, were receiving tolbutamide, and exhibited a markedly decreased insulin release following a carbohydrate meal compared to non diabetic controls.The present report deals with the alpha cell function in diabetic mice. The isolated perfused mouse pancreas was examined. Due to the hyperinsulinism in these obese animals the effect of high endogenous insulin release on pancreatic glueagon secretion was examined. Material and MethodsFor the present experiments diabetic mutant mice (C 57 BL/Ks-db/db ; Jackson Laboratory, Bar Harbour, Maine, USA), weighing 50--60 g, approximately 2--3 months old, and lean litter controls were used. Each group consisted of 5 animals.The mice were operated on after a 6 h fast. The pancreas was dissected under sodium pentobarbital anesthesia in a way similar to that already described for rats [23]. Arterial flow was achieved by cannulation * Supported by Deutsche Forschungsgemeinsehaft, Bad Godesberg. of the thoracic aorta. The perfusion medium consisted of an Umbreit buffer supplemented with 1% albumin (Fa. Behring Werke, Marburg) and equilibrated with 95% O2: 5% C02. The FFA content of the albumin buffer was < 50/~Lva]/1. A constant flow rate of 1 ml/ min was achieved by a pressure of about 40 m...

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Section: Discussionsupporting

confidence: 67%

“…All samples were assayed in one batch. Insulin (IMI) was measured immunologiea]ly [15]. A pork insulin standard curve was used, iodine 125 was used as tracer.…”

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confidence: 99%

Hyperglucagonemia of the isolated perfused pancreas of diabetic mice (db/db)

et al. 1973

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“…:-Arg-COOH, human sequence) (Peninsula Lab., Belmont, Calif., USA), were purified by high-performance liquid chromatography (HPLC) (Waters, Milford) on a reversed phase C-18 wide-pore column (Vydac RP 218) using a trifluoroacetic acid (TFA) / acetonitrile gradient system (bufferA: 0.1% TFA; buffer B: 0.1% TFA/29.9% water/70% acetonitrile). Islets were incubated with HPLC-pure peptides at concentrations of 0.25, 2.5, 25, 250 and 2500 nmol/1, respectively 9 Insulin release was measured by radioimmunoassay [12]. Results are expressed in mU.…”

Section: Methodsmentioning

confidence: 99%

Glucagon-like peptide-1 but not glucagon-like peptide-2 stimulates insulin release from isolated rat pancreatic islets

1985

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Summary. Glucagon-like peptide-1 and glucagon-like peptide-2 are encoded by the m-RNA of pancreatic preproglucagon. They show high conservation in different species and substantial sequence homology to glucagon. Because no definite biological activity of these peptides has been reported, we investigated the effect of synthetic C-terminally amidated glucagon-like peptide-t [1-36] and synthetic human glucagonlike peptide-2 [1-34] with a free C-terminus on insulin release from isolated precultured rat pancreatic islets in the presence of glucose. Glucagon-like peptide-1 stimulates insulin release at 10 and 16.7 mmol/1 glucose in a dose-dependent manner. Significant stimulation starts at 2.5 nmol/1 in the presence of 10 mmol/1 glucose and near maximal release is observed at 250 nmol/l, with approximately 100% increase over basal at both glucose concentrations. The peptide reaches 63% of the maximal stimulatory effect of glucagon. No stimulation occurs in the presence of 2.8 mmol/1 glucose. Glucagon-like peptide-2 has no effect on insulin secretion at any glucose concentration tested. It is concluded that glucagon-like peptide-t, in contrast to glucagon-like peptide-2, exhibits a glucose-dependent insulinotropic action on isolated rat pancreatic islets similar to that of glucagon and gastric inhibitory polypeptide.Key words: Glucagon-like peptide-t, glucagon-like peptide-2, insulin release, glucose dependency, isolated islets.Pancreatic preproglucagon m-RNA, the precursor of pancreatic glucagon, has been cloned and sequenced from different species using recombinant DNA-techniques [1][2][3][4][5]. Two other peptides have been found arranged in tandem on the same m-RNA in close proximity C-terminal to the glucagon precursor: glucagonlike peptide-I (GLP-1) and glucagon-like peptide-2 (GLP-2) comprising 36 and 34 amino acid residues, respectively. Both peptides show a different degree of sequence homology to pancreatic glucagon. The GLP-1 sequence is identical in the human, bovine and hamster precursor, whereas minor differences exist between the corresponding GLP-2 sequences. This substantial conservation in evolution and the close sequence homology to the glucagon molecule (GLP-I: 48% identical residues; GLP-2: 38%) indicates that GLP-1 and GLP-2 may play an important role of their own as hormones or local modulators. Recently they have been detected by specific radioimmunoassays in glucagonomas and in rat pancreatic islets [6], although they have not to date been isolated at the peptide level. Very little is known about a specific biological activity of these peptides. Hoosein and Gurd [7] could demonstrate a potent stimulation of rat hypothalamic and pituitary adenylate cyclase, whereas binding of glucagon to rat brain and liver membranes was not inhibited. GLP-1 may exert a weak stimulatory effect on exocrine pancreatic secretion in the rat [8].Suggesting a role in carbohydrate metabolism, we investigated the effect of synthetic GLP-I and GLP-2 on insulin release from isolated precultured rat pancreatic islets in th...

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“…During this period suitable aliquots for insulin determination were obtained at 0, 30, 60 and 120 min and immediately frozen until the hormone determination was performed. Immunologically measurable insulin (IMI) was determined following the procedure described by Melani et al [18].…”

Section: Methodsmentioning

confidence: 99%

The effect of serotonin on in vitro insulin secretion and biosynthesis in mice

1974

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Summary. The effect of serotonin on insulin secretion and biosynthesis was studied using isolated islets of mice. Serotonin produced a small stimulatory effect on insulin secretion when glucose was present in the incubation medium at a low concentration. On the other hand, an inhibition of insulin secretion was obtained with serotonin when glucose in the medium reached 3.0 mg/ml concentration. No significant effect of serotonin was obtained on insulin biosynthesis, neither in the presence of low nor with a high glucose concentration. These results suggest that the effect of this monoamine on insulin secretion is not mediated via its effect on insulin biosynthesis.

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Über die radioimmunologische Bestimmung von Insulin im Blut

Cited by 188 publications

References 13 publications

Hyperglucagonemia of the isolated perfused pancreas of diabetic mice (db/db)

Hyperglucagonemia of the isolated perfused pancreas of diabetic mice (db/db)

Glucagon-like peptide-1 but not glucagon-like peptide-2 stimulates insulin release from isolated rat pancreatic islets

The effect of serotonin on in vitro insulin secretion and biosynthesis in mice

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