Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate the in vivo effect of hyperglycemia per se on plasma free fatty acid (FFA) and glycerol concentrations, euglycemic and hyperglycemic clamp studies were performed in six overnight fasted dogs in the state of insulin deficiency produced by somatostatin (SRIF) infusion. The mean blood glucose concentrations during the steady-state (the second hour of each study) averaged 4.65 +/- 0.10 mmol/L in euglycemic clamp and 14.11 +/- 0.10 mmol/L in hyperglycemic clamp. During the SRIF infusion, plasma FFA concentrations increased from 0.32 +/- 0.05 mumol/mL at the basal state to 0.76 +/- 0.04 mumol/mL at the steady-state in euglycemic clamp and from 0.26 +/- 0.04 mumol/mL to 0.43 +/- 0.02 mumol/mL in hyperglycemic clamp. Plasma glycerol concentrations increased from the basal value of 0.07 +/- 0.01 mumol/mL to 0.15 +/- 0.01 mumol/mL during the steady-state in euglycemic clamp and from 0.06 +/- 0.01 mumol/mL to 0.08 +/- 0.01 mumol/mL in hyperglycemic clamp. The steady-state concentrations of plasma FFA and glycerol in hyperglycemic clamp were significantly lower than those in euglycemic clamp (P less than .001; respectively). These results suggest that hyperglycemia per se might decrease plasma FFA and glycerol concentrations at least in part by decreasing lipolysis in the acutely insulin-deficient dog.
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PMID:Hyperglycemia per se can reduce plasma free fatty acid and glycerol levels in the acutely insulin-deficient dog. 219 Nov 88

To determine the specific alteration in B-cell function caused by a somatostatin analog in man and to determine the effect of the induced insulin deficiency on insulin action, we administered octreotide (SMS 201-995; 50 micrograms twice daily) to nine healthy male subjects, aged 24-35 yr. B-Cell function was assessed by measuring the acute insulin response (AIR) to glucose (AIRglucose) at fasting glucose and to arginine (AIRarg) at glucose concentrations of fasting, approximately 14 and more than 28 mM after 2 (n = 7) and 8 days (n = 9) of octreotide. The AIRarg at more than 28 mM glucose (AIR500) is an estimate of B-cell secretory capacity, while the glucose level at which 50% of AIR500 occurs is termed PG50 and can provide an estimate of B-cell glucose sensitivity. Insulin sensitivity and the parameters describing glucose disposal were measured using Bergman's minimal model. Octreotide administration resulted in the development of mild fasting hyperglycemia, marked fasting hypoinsulinemia, as well as a marked reduction in AIRglucose [mean +/- SE; pretreatment, 260 +/- 48 pM; 1 day, 62 +/- 14 pM (P less than 0.005 vs. pretreatment); 8 days, 62 +/- 7 pM (P less than 0.005 vs. pretreatment)]. In addition, there was an associated marked reduction in iv glucose tolerance. While the AIRarg at fasting glucose (pretreatment, 233 +/- 27 pM; 2 days, 144 +/- 27 pM; 8 days 281 +/- 55 pM) and AIR500 (pretreatment 1000 +/- 178 pM; 2 days, 651 +/- 82 pM; 8 days, 1041 +/- 219 pM) remained unchanged, the AIRarg at 14 mM decreased significantly during octreotide [pretreatment 986 +/- 178 pM; 2 days, 363 +/- 62 pM (P less than 0.001 vs. pretreatment); 8 days, 623 +/- 130 pM (P less than 0.005 vs. pretreatment)], resulting in a rightward shift of the dose-response curve such that the estimated PG50 increased from 8.8 +/- 0.6 to 12.9 +/- 1.3 mM (P less than 0.05) after 2 days and was maintained for 8 days (11.2 +/- 0.8 mM; P less than 0.05 vs. pretreatment). Despite the development of marked insulin deficiency, the insulin sensitivity index (SI) did not change significantly (pretreatment, 11.34 +/- 1.59 x 10(-5); 1 day, 10.01 +/- 2.28 x 10(-5); 7 days, 9.65 +/- 1.69 x 10(-5) min-1/pM).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Treatment with a somatostatin analog decreases pancreatic B-cell and whole body sensitivity to glucose. 220 30

The effect of an intravenous infusion of glucose on plasma triglyceride (TG) concentration in fed rats was determined in order to partially elucidate the mechanism of diabetes-induced hypertriglyceridemia. Glucose infused at 8 mg/kg per min caused the plasma TG concentration to be elevated significantly when compared to controls infused with saline alone. In rats which were euglycemic (clamped, insulin infused at 2.5 mU/kg per min), plasma TG concentration remained constant throughout the glucose infusion period (8 mg/kg per min). Hyperglycemic rats infused with insulin (2.5 mU/kg per min) as well as with glucose (16 mg/kg per min) were also hypertriglyceridemic. Infusion of insulin alone did not change the concentration of plasma TG over a 150 min period. Glucose was also infused (8 mg/kg per min) with somatostatin (1 micrograms/kg per min) to block endogenous production of insulin. Somatostatin infusion did not suppress glucose-induced hypertriglyceridemia. For all treatments, the net change in TG concentration was found to positively correlate with the net change in plasma glucose concentration at 150 min after the infusions (r = 0.83, P less than 0.001). The higher TG concentration in the glucose infused, hyperglycemic clamp and glucose plus somatostatin groups reflected an increased rate of TG secretion, in the presence of a lower concentration of plasma free fatty acids. These results suggest that in a non-fasted state, acute hyperglycemia increases plasma TG by stimulating hepatic TG secretion, in a manner which is independent of either plasma insulin or free fatty acids levels.
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PMID:Effect of acute hyperglycemia on plasma triglyceride concentration and triglyceride secretion rate in non-fasted rats. 222 22

The effect of equimolar doses of GIP and GLP-1 (7-36amide) on insulin and somatostatin secretion in the isolated perfused rat pancreas was compared. At a perfusate glucose concentration of 70 mg/dl GLP-1 (7-36amide) 10(-9) and 10(-8) M and GIP 10(-9) M elicited a significant stimulation of insulin while GIP 10(-8) M and lower doses of both peptides (10(-11) and 10(-10) M) were ineffective. At elevated perfusate glucose levels of 150 mg/dl both peptides stimulated insulin release at 10(-11), 10(-10), 10(-9) and 10(-8) M but not at 10(-12) M. The insulin response at the higher glucose level was significantly greater compared to the effect of the same doses at normoglycemic conditions. Somatostatin release was stimulated significantly by GLP-1 (7-36amide) at 10(-10) and 10(-9) M at perfusate glucose level 70 mg/dl. At a glucose concentration of 150 mg/dl this effect was abolished. GIP did not alter somatostatin release at a perfusate glucose concentration of 70 mg/dl while at 150 mg/dl only the highest dose of GIP (10(-8) M) stimulated somatostatin release significantly. In conclusion, the present data demonstrate that in vitro in the rat pancreas both peptides are equally effective secretagogues of insulin release at normal and moderately elevated perfusate glucose levels. In contrast, somatostatin secretion is stimulated by GLP-1 (7-36amide) at normoglycemic conditions while only a rather high and presumably pharmacological dose of GIP is a stimulus of somatostatin secretion at moderate hyperglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of GLP-1 (7-36amide) and GIP on release of somatostatin-like immunoreactivity and insulin from the isolated rat pancreas. 223 56

We previously reported that neostigmine injected into the third cerebral ventricle stimulated adrenal secretion of epinephrine, secretion of glucagon from the pancreas, and direct neural innervation of the liver, resulting in hepatic venous plasma hyperglycemia in anesthetized fed rats. However, receptor type of these 3 mechanisms is not known. Therefore, we examined the effects of intraventricularly injected cholinergic or adrenergic antagonists on neostigmine-induced catecholamines in intact rats, glucagon secretion which is mediated by direct neural innervation of pancreas in bilateral adrenalectomized (ADX) rats, and hepatic venous hyperglycemia which is mediated by direct neural innervation of liver in ADX rats receiving constant infusion of somatostatin from femoral vein. Atropine injected into the third cerebral ventricle suppressed epinephrine secretion and dose-dependently inhibited hepatic venous hyperglycemia induced by neostigmine in intact rats. The neostigmine-induced glucagon secretion which occurs in ADX rats was suppressed by atropine. Atropine also prevented the neostigmine-induced hyperglycemia in ADX rats receiving constant somatostatin infusion through femoral vein (ADX-Somato rats). On the other hand, phentolamine, propranolol and hexamethonium showed no significant inhibitory effect on neostigmine-induced hyperglycemia, epinephrine and glucagon secretion in intact rats, glucagon secretion in ADX rats, or hyperglycemia in ADX-Somato rats. These results suggest that neostigmine-induced epinephrine and glucagon secretion and increased hepatic glucose output stimulated by direct neural innervation to liver is mediated by central muscarinic receptor in fed rats.
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PMID:Neostigmine-induced hyperglycemia is mediated by central muscarinic receptor in fed rats. 233 69

Acromegaly was diagnosed in 14 middle-aged to old cats of mixed breeding. Thirteen (93%) of the cats were male and one was female. The earliest clinical signs in the 14 cats included polyuria, polydipsia, polyphagia, all of which were associated with untreated diabetes mellitus. All developed severe insulin resistance within a few months; peak insulin dosages required to control severe hyperglycemia ranged from 20 to 130 U per day. Other clinical findings weeks to months after diagnosis included enlargement of one or more organs (e.g., liver, heart, kidneys, and tongue) (n = 14), cardiomyopathy (n = 13), increase in body size and weight gain (n = 8), nephropathy associated with azotemia and clinical signs of renal failure (n = 7), degenerative arthropathy (n = 6), and central nervous system signs (i.e., circling and seizures) caused by enlargement of the pituitary tumor (n = 2). The diagnosis of acromegaly was confirmed by demonstration of extremely high basal serum growth hormone concentrations (22 to 131 micrograms/l) in all cats. Computerized tomography disclosed a mass in the region of the pituitary gland and hypothalamus in five of the six cats in which it was performed. Two cats were treated by cobalt radiotherapy followed by administration of a somatostatin analogue (octreotide), whereas two cats were treated with octreotide alone. Treatment had little to no effect in decreasing serum GH concentrations in any of the cats. Eleven of the 14 cats were euthanized or died four to 42 months (median survival time, 20.5 months) after the onset of acromegaly because of renal failure (n = 2), congestive heart failure (n = 1), concomitant renal failure and congestive heart failure (n = 3), progressive neurologic signs (n = 2), persistent anorexia and lethargy of unknown cause (n = 1), the owner's unwillingness to treat the diabetes mellitus (n = 1), or unknown causes (n = 1). Results of necropsy examination in ten cats revealed a large pituitary acidophil adenoma (n = 10), marked left ventricular and septal hypertrophy (n = 7), dilated cardiomyopathy (n = 1), arthropathy affecting the shoulder, elbow, or stifle (n = 5), and glomerulopathy characterized by expansion of the mesangial matrix and variable periglomerular fibrosis (n = 10).
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PMID:Acromegaly in 14 cats. 240 66

We compared the effects of dexamethasone-induced insulin resistance on B-cell secretory performance in 12 low insulin responders (LIR) and in eight high insulin responders (HIR). A hyperglycemic clamp (120 minutes) was performed before and after the subjects had ingested dexamethasone 3 mg x 2 for 2 1/2 days. Fasting levels of blood glucose increased from 4.60 +/- 0.13 to 5.74 +/- 0.23 mmol/L after dexamethasone in LIR and from 4.37 +/- 0.18 to 5.26 +/- 0.13 mmol/L in HIR. Dexamethasone treatment increased fasting levels of total immunoreactive insulin (IRI), C-peptide, and proinsulin, as well as the proinsulin to IRI ratio to a similar degree in LIR and HIR. The amount of glucose infused to uphold hyperglycemia during the clamp decreased by 54% after dexamethasone in LIR and by 46% in HIR. Mean level of stimulated IRI during the clamp increased after dexamethasone by 43% in LIR and by 53% in HIR. Mean level of stimulated C-peptide increased by 11% (not significant) in LIR and by 24% in HIR. Mean level of stimulated proinsulin increased by 86% in LIR and by 93% in HIR. The effects of dexamethasone on insulin secretion varied among individuals, since steroid treatment failed to affect IRI responses to glucose in two LIR and two HIR. The magnitude of dexamethasone effects on secretion was not correlated to pre-dexamethasone insulin sensitivity as assessed by a somatostatin-insulin-glucose infusion test (SIGIT) or by M/I (glucose infused/insulin level) ratios of the control clamp.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of dexamethasone on glucose-induced insulin and proinsulin release in low and high insulin responders. 240 26

The splenic pancreas of 165 day old diabetic KKAy and age-matched nondiabetic C57BL/6 mice was examined by morphometry and immunocytochemistry at the light microscopic level and by radioimmunoassay to evaluate the morphology, surface area, endocrine cell composition and hormone content of the pancreatic islets. The insulin cells of the diabetic mice were severely degranulated and many of the glucagon, somatostatin and pancreatic polypeptide cells were displaced from the mantle to the core of the islet tissue where the non-insulin cells appeared to lose their continuity. The topography of some of the islets of KKAy mice was further deranged by acinar cells among the endocrine tissue. Morphometric analysis revealed that the surface area of the islets of KKAy mice was significantly expanded in comparison with that of C57BL/6 mice. The volume and numerical percents of the insulin cells were significantly increased whereas those of the glucagon and somatostatin cells were decreased in the KKAy mice. Since only the mean absolute number of insulin cells was elevated in the diabetic mice, the alteration in the relative proportions of the non-insulin cells and hypertrophy of the islets seemed to be a manifestation of insulin cell hyperplasia. Pancreatic insulin and somatostatin contents were markedly diminished in the islets of KKAy compared with those of C57BL/6 mice. These results demonstrate that the microscopic anatomy, endocrine cell populations and hormone content of the pancreatic islets are deranged in the KKAy mouse with severe hyperinsulinemia and hyperglycemia.
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PMID:Analysis of pancreatic islet cells and hormone content in the spontaneously diabetic KKAy mouse by morphometry, immunocytochemistry and radioimmunoassay. 244 17

The insulin release from isolated pancreatic islets grafted under the kidney capsule was examined by means of a modified kidney-perfusion technique. The grafts, consisting of 150 C57BL/6 or 250 C57BL/Ks mouse islets, were implanted syngeneically under the left kidney capsule of normoglycemic or alloxan-induced diabetic recipients 4 wk before the perfusion. In both mouse strains, islets grafted to normoglycemic animals showed an immediate distinct peak of insulin release when challenged with high glucose, whereas no response was observed from islets grafted to hyperglycemic mice. In a similar way in C57BL/Ks mice, arginine stimulated insulin release from the islet grafts in normoglycemic but not in hyperglycemic recipients. Insulin treatment of the diabetic recipients, however, partially normalized the insulin response to glucose. Islet grafts were removed in toto and analyzed for contents of insulin, glucagon, somatostatin, and DNA or rates of glucose-stimulated (pro)insulin biosynthesis. In both mouse strains, islets implanted into hyperglycemic animals contained significantly less insulin, and their rates of (pro)insulin biosynthesis were markedly decreased. Insulin treatment only marginally affected these parameters. The glucagon content of the grafted islets was unaffected by the hyperglycemia in both strains of mice, whereas a significant decrease in the somatostatin content was observed in the C57BL/Ks mice. We concluded that grafted islets exposed to prolonged hyperglycemic stress become functionally impaired in mice of both strains. Our perfusion technique of islet-graft-bearing kidneys in combination with biochemical studies on the removed grafts provides a suitable model for studies of the effects of prolonged hyperglycemia on islet beta-cell function.
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PMID:Effects of hyperglycemia on function of isolated mouse pancreatic islets transplanted under kidney capsule. 249 93

In previous studies on streptozotocin-diabetic rats, transplantation of 1,000 (but not of 400) pancreatic islets to the renal subcapsular space was followed within 10 days by near-normalization of the impaired insulin secretion and the hyperglycemia. The long-term effects were now studied by measuring insulin and glucagon secretion 3 months after transplantation of 1,000 collagenase-isolated islets in streptozotocin (70 mg/kg) diabetic rats. At this time, diabetic control rats showed marked hyperglycemia and hyperglucagonemia, whereas the basal glucose and glucagon levels had normalized in the transplanted rats. Furthermore, insulin secretion in response to glucose or arginine stimulation and glucagon secretion following arginine stimulation were normal in all transplant rats, but absent in all diabetic controls. Morphologically the transplanted islets in the renal subcapsular space appeared normal on hematoxylin-eosin staining and immunostaining with antisera directed against insulin, glucagon, somatostatin and chromogranin A/B. Thus the islet transplants normalized basal hyperglycemia and hyperglucagonemia and restored insulin and glucagon secretion on a long-term basis.
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PMID:Islet transplantation to the renal subcapsular space in streptozotocin-diabetic rats. Long-term effects on insulin and glucagon secretion. 251 96


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