Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to clarify the nature of the biological action of gut glucagon-like immunoreactivity (GLI), GLI was extracted from the mucosa of the canine intestine and purified by gel filtration and affinity chromatography. 1500 gm of the mucosa yielded approximately 7 gm of crude extract of GLI. This crude extract was applied to a column packed with Sephadex G-50 or Bio-Gel P-10 and two peaks were obtained, Peak I and II. Each peak was purified with affinity chromatography, bound to gamma-globulin of anti-glucagon rabbit-serum. In this step, the GLI was purified approximately 80 times in comparison with the crude extract. Peak I or Peak II, as well as pancreatic glucagon, was infused successively into the pancreaticoduodenal artery of the anesthetized dogs. When buffer solution or the Peak I GLI was infused, the plasma immunoreactive insulin in the pancreatic vein did not change significantly. In contrast, both the Peak II and pancreatic glucagon promoted insulin secretion from the pancreas. The results obtained in this experiment demonstrate the promotion of insulin release from the pancreas and suggest an important role of gut GLI in the absorption and metabolic processing of nutrients.
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PMID:Purification of canine gut glucagon-like immunoreactivity (GLI) and its insulin releasing activity. 93 62

Plasma immunoreactive glucagon (IRG) concentrations were measured in 36 patients with chronic renal failure (CRF) and 32 normal subjects. In addition, the components of circulating IRG were analyzed by gel filtration in the fasting state and after physiological stimuli. Fasting IRG was elevated (P less than 0.001) in CRF patients (534 +/- 32 pg/ml) compared with the levels found in healthy subjects (113 +/- 9 pg/ml). Oral glucose suppressed plasma IRG in CRF patients from a basal level of 568 +/- 52 to a nadir of 354 +/- 57 pg/ml (120 min). This degree of suppression (38%) was comparable to that found in normal subjects (basal = 154 +/- 20 to 100 +/- 23 pg/ml) at 120 min (35%). Intravenous infusion of arginine (250 mg/kg) resulted in a 71% rise in IRG in CRF patients and a 166% increase in normal subjects. Gel filtration of fasting plasma from CRF patients showed three major peaks. The earliest (A) was found in the void volume (mol wt greater than 40,000) and constituted 16.5 +/- 4.7% of the elution profile. The middle peak (B) eluted just beyond the proinsulin marker (approximately 9,000 mol wt) and constituted the largest proportion of the elution profile (56.5 +/- 3.4%). The third peak (C) coincided with the standard glucagon and [125I]glucagon markers (3,485 mol wt) and comprised 27.0 +/- 4% of the IRG profile. In contrast, only peaks A and C were found in fasting plasma of normal subjects (53.6 +/- 10.4% in A and 46.4 +/- 10.4 in C). After oral glucose, glucagon immunoreactivity in the 3,500 mol wt peak (C) was markedly suppressed, while the B peak in patients with CRF declined to a lesser extent. The A peak in both groups was unchanged. After an arginine infusion only the C peak increased in both groups of subjects. Gel filtration of plasma in 3 M acetic acid gave similar profiles to those obtained in glycine albumin buffer. Exposure of serum to trypsin indicated that the B and C peaks were digestible, while the A peak was resistant to the action of the enzyme. In one sample, peak C increased after a 2-h exposure of serum to trypsin. We conclude that circulating IRG in normal subjects and patients with CRF is heterogenous. The hyperglucagonemia of renal failure is largely due to an increase in IRG material of approximately 9,000 mol wt, consistent with proglucagon, although the 3,500 mol wt component is also considerably elevated (threefold). The significance of circulating IRG levels should be interpreted with caution until the relative biological activity of the three components is established.
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PMID:Heterogeneity of plasma glucagon. Circulating components in normal subjects and patients with chronic renal failure. 95 99

Analysis of the plasma from a totally pancreatectomized patient, with antiserum 30 K, has demonstrated basal glucagon immunoreactivity (GIR) levels in the normal range (80-110 pg/ml). Neither i. v. arginine nor oral glucose affected these GIR values, thus indicating the absence of functioning pancreatic or gastrointestinal A-cells. Furthermore, filtration of whole plasma on Bio Gel P-30 showed no GIR in the 3500 MW elution volume. GIR was found to be distributed in two peaks. One peak eluted in the protein region, similarly to "big plasma glucagon" (BPG), and the second peak appeared after the glucagon-I125 marker. The protein-sized moiety was not absorbable by charcoal, and on Sephadex G-100 it eluted within the globulin region. When subjected to trypsin treatment, it yielded smaller GIR fractions. According to these criteria, it can be assumed that this component is identical to BPG. Therefore, an extrapancreatic source for BPG is suggested. On the other hand, the presence of fasting hyperglycaemia in this patient indicates that insulin deficiency by itself suffices to raise blood sugar to diabetic levels.
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PMID:Plasma glucagon immunoreactivity in a totally pancreatectomized patient. 100 50

Viable pancreatic islets were isolated from the pancreas of humans using modifications of the collagenase digestion and Ficoll gradient techniques. Gel filtration of tissue extracts following islet incubation in the presence of 3H- tryptophan indicated that radioactivity becomes incorporated into at least two islet proteins. The larger of the two (LGI) has the approximate molecular size of proinsuiln and the smaller coelutes with glucagon as determined by column standardization. Radioimmunoassay of the gel filtration eluate for glucagon revealed that both molecules have glucagon immunoreactivity. Gel filtration in the presence of 8M urea did not alter the elution pattern of the LGI molecule. Polyacrylamide gel electrophoresis was performed on these glucagon immunoreactive molecules. The 3H radioactivity and the glucagon immunoreactivity of the smaller molecule were found to co-migrate electrophoretically with crystalline porcine glucagon and monodesamidoglucagon. With electrophoresis at high pH the electrophoretic mobility of the LGI molecule proved to be lower than that of glucagon. Partial tryptic degradation of the human LGI molecule yields 3H-tryptophan labeled products having charge and immunologic characteristics indistinguishable from porcine glucagon and monodesamidoglucagon. Although further investigation is indicatend may thus serve as a precursor or an intermediate in human glucagon biosynthesis.
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PMID:Glucagon biosynthesis in human pancreatic islets: preliminary evidence for a biosynthetic intermediate. 109 15

Filtration of basal plasma from normal, alloxan-diabetic, and depancreatized dogs on Bio Gel P-10 yielded four glucagon-immunoreactive fractions. One of them appeared in the true glycagon area with the glucagon-125I (3500 mol vt). Of the other three, one appeared in the void volume (greater than 20000 mol wt), another just before the insulin-125I (congruent to 9000 mol wt), and the last one close to the salt peak (less than 2000 mol wt). The increase of total plasma glucagon immunoreactivity observed in depancreatized and alloxan diabetic dogs was mainly due to an increase in the 3500 and 9000 molecular-weight fractions. Arginine infusion in depancreatized dogs caused an increase in the 3500 molecular-weight fraction. Somatostatin or insulin infusion in depancreatized and alloxan-diabetic dogs resulted in disappearance of the 3500 molecular-weight fraction.
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PMID:Heterogeneity of plasma glucagon immunoreactivity in normal, depancreatized, and alloxan-diabetic dogs. 115 74

We report on a Japanese girl with short stature, malar hypoplasia, up-slanting palpebral fissures, blue sclerae and thin, stiff and slightly brownish hair. Short stature started in utero and her psychomotor development was normal. Menarche appeared at 13 years 8 months. Height at 14 years 5 months was 132 cm (-4.6 SD). Her growth hormone (GH) sleep pattern and responses to insulin, L-dopa, arginine, propranolol-glucagon and growth hormone-releasing hormone were normal. Plasma insulin-like growth factor I (IGF-I) was high (2170-4860 units/l) and increased from 4860 to 7080 units/l 20 h after biosynthetic GH injection. Gel infiltration patterns of the free and protein-bound IGF-I in plasma from the patient were not different from the controls; IGF-I fraction of the high and low molecular weight binding protein and the non-protein bound fraction were 75.5%, 15.8% and 8.7%, respectively. IGF-I from the patient showed normal bioactivities when determined by [35S]sulphate and [3H]thymidine uptake into cultured rat chondrocytes, and by [3H]thymidine and [3H]alpha-aminoisobutyric acid uptake into the patient's skin fibroblasts. IGF-I binding to cultured skin fibroblasts from the patient was comparable to that of controls. These results suggest that tissue specific defects of IGF-I receptors may be the cause of increased IGF-I levels in the patient.
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PMID:Short stature with normal growth hormone and elevated IGF-I. 139 82

Gut glucagon-like immunoreactivity (GLI), a supposed intestinal growth factor in the plasma and gastrointestinal tract, and weight of the gastrointestinal tract, an intestinal growth indicator, were examined in ventromedial hypothalamic (VMH)-lesioned rats 1 week after VMH lesions. Postprandial plasma gut GLI in VMH-lesioned rats was significantly higher than that in control rats. The content of gut GLI in all gastrointestinal sections except the duodenum in VMH-lesioned rats was significantly greater than that in control rats. Gel chromatography in the lower portion of the small intestine in which GLI content was the highest of all sections revealed the same pattern in both VMH-lesioned and control rats with two peaks of similar molecular size. Weight of all gastrointestinal sections except the cecum in VMH-lesioned rats significantly increased. These results demonstrated that both gut GLI secretion and production were enhanced in VMH-lesioned rats. The elevated gut GLI release may accelerate growth of the gastrointestinal tract in these animals.
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PMID:Elevated content and secretion of gut GLI in VMH-lesioned rats. 150 51

Postprandial glucagon-like peptide-1 (GLP-1), pancreatic glucagon, and insulin were measured in 27 tumor-free patients 43 months (median) after total gastrectomy and in four controls using a 99technetium-labeled 100-g carbohydrate solid test meal. Emptying of the gastric substitute was measured by scintigraphy. Fourteen patients suffered from early dumping symptoms, and five of them also reported symptoms suggestive of reactive hypoglycemia (late dumping). The median emptying half-time (T1/2) of the gastric substitute was 480 sec. Sigstad's dumping score was 8.5 +/- 1.6 (mean +/- SE) in patients with rapid emptying (T1/2 less than 480 sec), and 3.0 +/- 1.5 in patients with slow emptying of the gastric substitute (P = 0.02). The peak postprandial concentration of GLP-1 was 44 +/- 20 pmol/liter in controls, 172 +/- 50 in patients without reactive hypoglycemia, and 502 +/- 116 in patients whose glucose fell below 3.8 mmol/liter during the second postprandial hour. Plasma GLP-1 concentrations peaked at 15 min, and insulin concentrations at 30 min after the end of the meal. A close correlation between integrated GLP-1 responses and integrated insulin responses (r = 0.68) was observed. Multiple regression revealed that three factors were significantly associated with the integrated glucose concentrations during the second hour (60-120 min): Early (first 30 min) integrated GLP-1 (inverse correlation; P = 0.006), age (P = 0.006), and early integrated pancreatic glucagon (P = 0.005). There was a close (inverse) relationship of T1/2 with early integrated GLP-1 and pancreatic glucagon, but not with insulin. Gel filtration of pooled postprandial plasma of gastrectomized individuals revealed that all glucagon-like immunoreactivity eluted at Kd 0.30 (Kd, coefficient of distribution), the elution position of glicentin. Almost all of the GLP-1 like immunoreactivity eluted at Kd 0.60, the elution position of gut GLP-1. The authors contend that GLP-1-induced insulin release and inhibition of pancreatic glucagon both contribute to the reactive hypoglycemia encountered in some patients following gastric surgery. Rapid emptying seems to be one causative factor for the exaggerated GLP-1 release in these subjects.
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PMID:Emptying of the gastric substitute, glucagon-like peptide-1 (GLP-1), and reactive hypoglycemia after total gastrectomy. 191 56

A new active peptide was purified from the acid-alcohol extract of pork pancreas. It markedly suppressed the insulin activity detected by either in vivo mouse convulsion assay or in vitro free-fat cell assay. When the extract was subjected to chromatography on a carboxymethylcellulose column, the insulin fraction completely passed through the column, whereas the glucagon fraction was absorbed. The fact that the total apparent biological activity of insulin in the exclusive eluate was higher than in the original extract and the insulin radioimmunoactivity remained unchanged led to the discovery of a potent insulin inhibitor in the extract. The inhibitor was separated from glucagon and insulin in the extract by ion-exchange chromatography on a carboxymethylcellulose column followed by gel filtration on a Bio-Gel P-6 column and finally purified by reverse-phase high-performance liquid chromatography (HPLC) on a C-18 column. The antagonistic effect of this inhibitor on insulin was dose dependent with an ED50 of 2 x 10(-10) M, which was the same level used for insulin in vitro assay (1.7 x 10(-10) M). Amino acid analysis of the inhibitor showed that it was rich in arginine and glycine. It was estimated to be approximately 3000 Mr. The NH2-terminal of the peptide was proved to be blocked because it could not be degraded by Edman degradation. Based on the physicochemical and biochemical characteristics of the inhibitor and compared with other active peptides known to be in the pancreas, the inhibitor is probably a new active peptide that might play an important role in homeostasis of carbohydrate metabolism.
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PMID:Purification and preliminary characterization of new peptide inhibitor of insulin from pork pancreas. 193 26

Degradation of [125I]iodoglucagon during RIA of glucagon would result in erroneously high values for immunoreactive glucagon (IRG). Normal rat plasma was found to have high activity for glucagon degradation that was not suppressed by the aprotinin and EDTA routinely added to the RIA system. About 30% of the added radioactive glucagon was degraded during RIA in assay mixture at pH 7.4 containing 0.2 ml normal rat plasma, and the IRG value was calculated to be 150-180 pg/ml plasma. The degradation was completely inhibited by addition of 2 mM p-chloromercuriphenyl sulfonate (PCMS) plus 0.25 mM leupeptin as protease inhibitors, and in their presence the IRG value was about 80 pg/ml. The glucagon-degrading activity was about half as much in assay mixture at pH 8.8 as in that at pH 7.4, but the degradation still affected the accuracy of IRG values. When rat plasma was incubated with [125I]iodoglucagon in the assay conditions used for RIA and then subjected to Bio-Gel P-6 filtration, three new peaks of radioactivity were found in low mol wt fractions, with decrease in the peak corresponding to [125I]iodoglucagon, whereas on similar treatment in the presence of PCMS and leupeptin all the radioactivity was recovered in the glucagon fraction. The average recoveries of authentic glucagon as IRG in the absence and presence of the inhibitors were less than 60% and more than 90%, respectively. These findings indicate that determination of plasma IRG in rats by RIA with assay mixture containing aprotinin gives spuriously high values owing to degradation of the radiotracer, and that PCMS and leupeptin should be added to the sample and assay mixture to prevent this degradation.
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PMID:Degradation of [125I]iodoglucagon by normal rat plasma in radioimmunoassay mixture containing aprotinin and its prevention by p-chloromercuriphenyl sulfonate and leupeptin. 242 96


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