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)

After a 0100-0300 h nadir, the insulin requirements to maintain blood glucose at 90-110 mg/dl increase substantially in the prebreakfast (0600-0800 h) period in some insulin-dependent diabetic patients (IDDMs). Early insulin-like and delayed insulin-antagonistic effects of physiologic early morning increases in growth hormone (hGH) secretion may account for this variability of overnight insulin requirements. To assess the role of hGH, we studied five IDDMs using a closed-loop insulin infusion device (Biostator, GCIIS). Either saline (C) or somatostatin plus glucagon (SRIF + G) was infused during separate overnight (2400-0800 h) study periods. An infusion of hGH from 2400 to 0130 h was added to SRIF + G infusion during an additional study period (SRIF + G + hGH). In comparison to 0100-0300 h, mean insulin infusion rates required to maintain blood glucose values between 105 and 120 mg/dl during the prebreakfast period increased by 66 +/- 25% during C, and 42 +/- 12% during SRIF + G when serum growth hormone was suppressed to less than or equal to 0.75 ng/ml. During SRIF + G + hGH, the mean prebreakfast insulin infusion rate increased by 42 +/- 11% with a mean peak hGH level of 14.7 +/- 5.4 ng/ml at 0130 h. Mean plasma free insulin levels remained constant during the night despite the significantly higher insulin infusion rates between 0600 and 0800 h. During SRIF + G, insulin requirements remained constant overnight before 0600 h, whereas during both C and SRIF + G + hGH conditions, a nadir was noted between 0100 and 0300 h.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of growth hormone on overnight insulin requirements in insulin-dependent diabetes. 285 43

Tissue extracts of discrete lobes of chicken pancreas were assayed for pancreatic polypeptide (PP), glucagon, somatostatin (SRIF), and insulin by radioimmunoassay. Concentrations of all pancreatic hormones except PP were highest in the splenic lobe. PP concentration was greatest in the inferior portions of the three major lobes. There is a reciprocal relationship between PP and glucagon concentration in chicken pancreas. The results with extracts were substantiated by cell frequency measurements using immunocytochemical methods.
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PMID:Regional distribution of pancreatic polypeptide and other hormones in chicken pancreas: reciprocal relationship between pancreatic polypeptide and glucagon. 286 49

The present study was designed to compare, in lean and obese nondiabetic subjects, basal and postprandial levels of peripheral venous plasma insulin, glucagon, gastrin, pancreatic polypeptide (PP), glucose, triglycerides, and somatostatin-like immunoreactivity (SLI) during the infusion of synthetic somatostatin-14 or saline. Thirty-five minutes before the ingestion of the test meal, an infusion of synthetic somatostatin-14 was started at a rate of 0.5 ng/kg X min and was increased to 1.0 ng/kg X min 30 min after consumption of the meal and lasted for another 90 min. During the infusion of saline, basal peripheral vein levels of insulin, gastrin, and triglycerides were elevated in obese subjects, whereas basal plasma SLI levels were significantly lower compared with the lean controls. Basal glucagon and PP levels were similar in both groups. After the ingestion of the meal, augmented concentrations of insulin and gastrin were observed in the obese subjects, whereas postprandial SLI and PP levels were reduced. Chromatography of fasting plasma revealed all measurable SLI to be confined to the void volume fractions of a Bio-Gel P-10 column. The rise in SLI after the meal was due to an increase of SLI co-eluting with somatostatin-28 and somatostatin-14. During the infusion of somatostatin, only basal insulin levels were significantly lower in the obese subjects, whereas no change of any basal hormone level was observed in the lean group. During the infusion of somatostatin, SLI levels were elevated by 20-30 pg/ml in both groups compared with the saline controls. During the infusion rate of 0.5 ng/kg X min, only postprandial PP levels were reduced significantly in the obese group, while all the other parameters were unaffected in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of low-dose somatostatin infusion on pancreatic and gastric endocrine function in lean and obese nondiabetic human subjects. 286 Nov 27

Five antisera against insulin (Ins), glucagon (Glu), somatostatin (SRIF), met-enkephalin (met-enk), and serotonin (5-HT) were used for immunofluorescence detection of endocrine cells in pancreas and gastrointestinal tract (GIT) of the European eel (Anguilla anguilla L.) at three stages of development (leptocephalic larva, glass-eel, and adult eel). Comparable distribution of endocrine cells was observed for adults and glass-eels. In their pancreatic islets, positive immunoreactions were obtained only for Ins, SRIF, and Glu; this later was also present in the pancreatic ducts. 5-HT cells were present throughout the GIT. SRIF cells were situated mostly in the stomach and less in the intestine. Met-enk cells were abundant in the pyloric cecum, but less frequent in the intestinal mucosa. Glu cells were present only in the intestine. No insulin-immunoreactive cells could be detected in the GIT. The pancreatic islets of leptocephalic larvae exhibited a strong reaction for SRIF, a weak reaction for Glu, and none at all for Ins, met-Enk, or 5-HT. The GIT of these larvae contained numerous met-enk cells, mainly in the foregut. In the fore- and midgut, cells exhibited a weak fluorescence after treatment with Glu antiserum. No positive immunoreactive cells were observed with 5-HT, SRIF, or Ins antisera.
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PMID:Detection of endocrine cells by immunofluorescence method in the gastroenteropancreatic system of the adult eel, glass-eel, and leptocephalic larva (Anguilla anguilla L.). 286 Nov 42

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.
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PMID:Control of plasma levels of growth hormone, glucagon and insulin in ducklings: roles of free fatty acids and somatostatin. 286 14

The glucagon response to insulin hypoglycaemia is frequently reduced in patients with IDDM. In the present study arginine infusion, thought to act directly on the islet cells, was used to stimulate somatostatin (SRIF) and glucagon in IDDM without residual B-cell function. Thirteen IDDM patients' were compared with 13 sex- and age matched normal controls following an arginine infusion. The plasma SRIF concentrations in the 'IDDM group' and normal controls increased from 24.2 +/- 2.5 to 31.1 +/- 3.9 pmol/l (P less than 0.01) and 19.7 +/- 1.7 to 23.9 +/- 3.4 pmol/l respectively after 10 min (P less than 0.01). The plasma glucagon concentrations increased from 27 +/- 4.7 to 176 +/- 23.1 pmol/l (P less than 0.01) and 36 +/- 5.0 to 302 +/- 31.9 pmol/l (P less than 0.01) respectively after 20 min. Thus, in long standing IDDM without residual B-cell function, increased plasma SRIF concentrations are found and the glucagon response to arginine is reduced. The last observation further explains why these patients are especially vulnerable to hypoglycaemia.
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PMID:Increased peripheral venous somatostatin concentration and decreased glucagon response to arginine in patients with insulin dependent diabetes mellitus without residual B-cell function. Increased plasma SRIF in IDDM. 286 13

Based upon the clinical finding that a Merck somatostatin-14 (S-14) analog induced steatorrhea in man, we sought to develop animal models to study the effects of S-14 and a series of synthetic analogs on absorption. Rats were trained to eat a diet (preweighed) containing 15% fat. Following the feeding period, the remaining diet was removed and the amount consumed recorded. This food conditioning of the rats was continued until the rats consumed approximately 15 g of the diet per day. Feces were collected and weighed prior to feeding periods. On test days, S-14 or analogs were administered sc to rats immediately prior to feeding. For each compound tested, fat absorption decreased in dose-dependent fashion. For example, S-14 at 0.5 mg/kg did not increase % of dietary fat in feces (% DFF). At 1.0 mg/kg, S-14 increased % DFF from 7.9 to 10.2 (p less than 0.01, pretest day vs test day), and at 10 mg/kg S-14, % DFF increased from 9.1 to 12.8 (p less than 0.001). For each analog, the subcutaneous dose required to decrease fat absorption in rats was several orders of magnitude higher than the intravenous dose required to inhibit insulin and glucagon. Moreover, the threshold for production of statistically significant increases in fecal fat differed among analogs when compared to their endocrine potencies. One analog administered in the model for 14 days was shown to produce consistent fat malabsorption throughout the entire test period; however, this lipid malabsorption was substantially more pronounced on the first three days of the treatment period. When the compound was not administered on day 15, the % DFF significantly decreased. In an attempt to develop a system more suitable for rapid screening, pancreatic secretagogues such as secretin or cholecystokinin, were administered intravenously to anesthetized rats whose duodena had been cannulated and perfused to enable collection of pancreatic secretions. Total amylase, lipase, and protein were determined in single animals in response to a secretagogue, both before and after iv pretreatment by S-14 or an analog. Pancreatic enzyme secretion in response to sequential secretagogue-stimulation was found to be reproducible for up to three injections and behaved in a dose-dependent fashion. In general, secretagogue-induced increases in amylase, lipase, and total protein were comparable. Pretreatment with the S-14 analogs substantially inhibited secretagogue-induced pancreatic exocrine secretion and was dose-dependent.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The effects of somatostatin and selected analogs on lipid absorption in animals. 286 42

Glucose disappearance after an oral or intravenous challenge is a function of the effects of both endogenously secreted insulin and of glucose itself. We previously introduced the term "glucose effectiveness," or SG, defined as the ability of glucose per se to enhance its own disappearance independent of an increment in plasma insulin. The present investigation, performed in conscious dogs, was undertaken to quantify this glucose effect by minimal-model-based analysis of insulin and glucose dynamics after a frequently sampled intravenous glucose tolerance test (FSIGT). The values from the standard FSIGT were then compared with direct measurements obtained from experiments in which the dynamic insulin response to glucose was suppressed with somatostatin (SRIF). In addition, we examined SG values from the modified FSIGT protocol, which involves both glucose and tolbutamide injections. Protocol l (N = 9): FSIGTs were performed and the glucose and insulin data were analyzed by computer. KG was 2.65 +/- 0.28 min-1, S1 was 4.09 +/- 0.34 X 10(4) min-1/(microU/ml), and SG was 0.033 +/- 0.004 min-1. Protocol II (N = 6): FSIGTs were performed on animals in which SRIF was infused (0.8 micrograms/min X kg) to obliterate the dynamic insulin response to glucose injection. Before the FSIGt, insulin and glucagon were infused intraportally to reattain basal glycemia. Without dynamic insulin, KG was reduced to 0.96 +/- 0.18 min-1 (P less than 0.0001). However, SG, estimated from the exponential rate of fall of plasma glucose in the absence of dynamic insulin, was similar to the standard FSIGTs: 0.025 +/- 0.004 (P greater than 0.25). Protocol III (N = 6): modified FSIGTs were performed using glucose and tolbutamide injections for a better estimate of model parameters. Model parameters Sl and SG, and the KG were not different from standard FSIGTs (P greater than 0.3). In fact, the value of SG (0.028 +/- 0.003 min-1) was nearly identical to the direct measure from protocol II. Therefore, the effect of glucose per se on glucose decline, estimated by modeling the standard and modified FSIGTs, was confirmed by a direct measurement with the endogenous insulin response suppressed with SRIF. Also, the time course of the insulin effect to enhance net glucose disappearance from plasma [Ieff(t)] was calculated from the data of protocol II, and was the same as the time course predicted by the model. These studies demonstrate the ability of the computer modeling approach to separate insulin-dependent and glucose-dependent glucose disappearance, and represent a direct confirmation of the minimal model.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Importance of glucose per se to intravenous glucose tolerance. Comparison of the minimal-model prediction with direct measurements. 286 97

Fractions of isolated epithelial cells were harvested from a segment of porcine jejunum by ten successive incubations with a chelating buffer. The cell fractions showed a progressive decrease in the activity of the brush-border enzymes, alkaline phosphatase and sucrase, with increasing incubation number but a progressive increase in the ability to incorporate labelled thymidine into DNA. Fractions enriched in cells from the crypt region (fractions 9 and 10) contained higher concentrations per mg protein of somatostatin-like immunoreactivity (1.8-fold), glucagon-like immunoreactivity (5.3-fold) and serotonin (3.0-fold) than fractions enriched in cells from the villus tip (fractions 1 and 2). Analysis of extracts of the fractions by gel filtration/radioimmunoassay showed that somatostatin-28 represented the predominant molecular form of somatostatin-like immunoreactivity in all cell fractions but the relative proportion of somatostatin-14 (and related metabolites) to somatostatin-28 was significantly higher (P less than 0.05) in fractions enriched in villus cells (fraction 1 and 2) than in fractions enriched in crypt cells (fractions 5-10). This result suggests that metabolism of somatostatin-28 to somatostatin-14 takes place during migration of the D cell from the crypt base to the villus tip. Heterogeneity in the somatostatin-14 region of the chromatograms indicates that the peptide may be further metabolized by the action of aminopeptidases.
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PMID:Conversion of somatostatin-28 to somatostatin-14 during maturation of epithelial cells in the porcine jejunum. 286 59

Ten acromegalic patients, 28-71 years old, were compared with 10 normal controls, 21-39 years old. In another study, 7 patients with active acromegaly, 19-70 years old, were investigated before and 4-9 months following transsphenoidal adenectomy and radiation. They were all investigated following an arginine infusion (0.5 g/kg/20 min). Although the mean plasma somatostatin (somatotrophin release inhibiting factor (SRIF] was somewhat higher in acromegalic patients compared to normal controls (mean basal values 21 +/- 3.8 and 16.6 +/- 2.1 pmol/l, respectively), the difference was not significant. The patients had higher serum insulin (peak values 118 +/- 23.9 and 63 +/- 11.8 mU/l, respectively) and lower plasma glucagon (peak values 171 +/- 29.0 and 310 +/- 52.7 pmol/l, respectively). Plasma SRIF increased during arginine infusion, but the concentrations were similar before and following the operation (mean basal values 18.2 +/- 2.6 and 15.2 +/- 2.3 pmol/l, respectively). Serum insulin was significantly higher before the operation (peak values 154 +/- 38.8 and 91 +/- 24.9 mU/l, respectively). Plasma glucagon was similar before and after the operation (peak values 143 +/- 23.4 and 127 +/- 22.7 pmol/l, respectively). Plasma SRIF is similar in active acromegaly and normal controls, and in acromegaly before and following treatment, despite differences in serum growth hormone (GH), serum insulin and plasma glucagon. This points towards a modulating role for GH on plasma SRIF, possibly by affecting the other islet cell hormones.
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PMID:Somatostatin, insulin and glucagon after arginine stimulation in active and treated acromegaly. 286 32


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