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)

We used isolated islets of lean and obese Zucker rats to determine whether inhibitory pathways mediated by pertussis toxin-sensitive guanyl nucleotide-binding (Gi) proteins contribute to hyperinsulinemia in obese rats. Epinephrine (10(-4) M) and somatostatin (10(-7) M) inhibited insulin secretion by +/- 75% in lean and fa/fa rats. Overnight culture of islets with pertussis toxin (300 ng/ml) enhanced insulin release more in lean (+/- 120%) than obese (+/- 60%) rats. In lean rats incubation of pertussis toxin-treated islets with epinephrine resulted in lower immunoreactive insulin release (p = 0.0005) than pertussis toxin-treated islets without epinephrine. However, in obese rats pertussis toxin treatment reversed this inhibition. Pertussis toxin completely reversed inhibition by somatostatin in both phenotypes. Galanin had no effect on insulin secretion. Cellular cAMP content was similar in lean and obese rats. Inhibitory hormones had no effect on cAMP production. We conclude that islets of obese rats respond normally to inhibitors of insulin release. Reversal of somatostatin-induced inhibition by pertussis toxin indicates normal function of Gi in obese rats. A subtle difference in sensitivity to pertussis toxin between lean and obese islets was noted.
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PMID:Effect of pertussis toxin on islet insulin secretion in obese (fa/fa) Zucker rats. 170 22

We performed euglycemic clamp studies with labeled glucose to measure insulin's effect on hepatic glucose output (HGO) and peripheral glucose clearance in eight conscious mobile spontaneously hypertensive rats (SHR) and eleven normotensive Wistar-Kyoto (WKY) rats age 9-10 wk. Systolic blood pressure was elevated in the SHR (P less than 0.001), whereas means of 12-h-fasted plasma insulin (P greater than 0.4), glucose (P greater than 0.07), HGO (P greater than 0.25), and glucose clearance (P greater than 0.2) did not differ significantly between groups. Infusions of human insulin into SHR and WKY rats (1 and 1.5 mU.min-1.kg-1, respectively) during concomitant somatostatin administration reestablished basal insulinemia in both groups. Neither HGO (P greater than 0.15) nor glucose clearance (P greater than 0.3) differed significantly between SHR and WKY rats under those conditions. Somatostatin plus higher-dose insulin infusions (4 mU.min-1.kg-1 in SHR and 3 or 6 mU.min-1.kg-1 in WKY rats) resulted in physiological hyperinsulinemia in all rats. Insulin sensitivity, calculated as the increase in glucose clearance effected by an increase in circulating insulin during higher-dose insulin infusions, did not differ significantly between SHR and WKY groups (P greater than 0.3). HGO was completely suppressed in SHR and WKY rats during the higher-dose insulin infusions. Our data indicate that hypertension is present in SHR at an age when insulin-mediated glucose disposal is not different from age-matched WKY rats. These findings do not support a role for peripheral insulin resistance in the genesis of hypertension in SHR.
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PMID:Hypertension without peripheral insulin resistance in spontaneously hypertensive rats. 173 45

Patients with hypertension have been shown to be resistant to insulin-stimulated glucose uptake and to be both hyperinsulinemic and hypertriglyceridemic compared with matched normotensive control groups. These abnormalities are present before the institution of antihypertensive therapy and do not necessarily improve when blood pressure is effectively lowered. Insulin resistance, hyperinsulinemia, hypertriglyceridemia, and high blood pressure can be produced in fructose-fed Sprague-Dawley rats, but the development of these changes is inhibited by exercise training or somatostatin infusion. Furthermore, insulin-stimulated glucose uptake is lower in spontaneously hypertensive rats (SHRs) than Wistar-Kyoto rats, and this is associated with higher plasma triglyceride concentrations and blood pressure. In addition, a defect in insulin-stimulated glucose uptake can be shown in adipocytes isolated from SHRs, and the greater the degree of in vitro insulin resistance, the higher the plasma insulin concentration and blood pressure. These data strongly support the view that abnormalities of insulin and lipid metabolism are associated with high blood pressure in both patients and rodent models of experimental hypertension. In the latter context, endogenous hyperinsulinemia and hypertriglyceridemia are risk factors for coronary heart disease. The fact that antihypertensive treatment has not focused on correcting these metabolic abnormalities may explain why it has been difficult to show that lowering blood pressure decreases the risk of coronary heart disease. It can be argued that abnormalities of carbohydrate and lipoprotein metabolism play a role in both the etiology of hypertension and the clinical course of hypertensive patients.
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PMID:Relationship between insulin resistance and hypertension. 174 55

Hypoglycemia with hyperinsulinism persisted in a newborn weighing 6410 g despite treatment with high doses of diazoxide and glucagon, as well as infusions of glucose and somatostatin. A subtotal pancreatectomy was performed after nesidioblastosis had been diagnosed on the basis of the laboratory findings. Due to the persistence of therapy-resistant hypoglycemia, a total pancreatectomy preserving the duodenum and the bile duct was done 6 weeks later. With insulin and pancreatic enzyme substitution the now 6-year, 9-month-old child has shown normal, age, appropriate development.
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PMID:Total pancreatectomy in a case of nesidioblastosis due to persisting hyperinsulinism following subtotal pancreatectomy. 190 2

Insulin receptor function, glycogen synthase activity, and activation by phosphatases were studied in biopsies of human skeletal muscle under conditions of hyperglycemia and/or hyperinsulinemia for 150 minutes. Twenty-one healthy volunteers underwent either (A) a hyperinsulinemic, euglycemic clamp (serum insulin, 160.0 +/- 7.7 mU/L; plasma glucose, 4.9 +/- 0.1 mmol/L; n = 9), (B) a hyperglycemic clamp during normoinsulinemia (serum insulin, 18.1 +/- 3.3 mU/L; plasma glucose, 12.9 +/- 0.2 mmol/L; n = 6), or (C) a combined hyperinsulinemic, hyperglycemic clamp (serum insulin, 158.3 +/- 15.0 mU/L; plasma glucose, 11.4 +/- 0.8 mmol/L; n = 6). During all studies, the endogenous insulin secretion was inhibited with somatostatin. Insulin binding and kinase activity of insulin receptors solubilized from vastus lateralis muscle biopsies were unaffected by hyperglycemia and/or hyperinsulinemia. Hyperinsulinemia activated the muscle glycogen synthase with a decrease in the half-maximal activation constant (A0.5) for glucose-6-phosphate (G6P) from 0.53 +/- 0.04 to 0.21 +/- 0.02 mmol/L (study A, P less than .02) and from 0.53 +/- 0.06 to 0.19 +/- 0.05 mmol/L (study C, P less than .03). In addition, the rate of glycogen synthase activation by phosphatases increased from 0.078 +/- 0.017 to 0.134 +/- 0.029 U/min/mg protein (study A, P less than .03) and from 0.082 +/- 0.013 to 0.145 +/- 0.033 U/min/mg protein (study C, P = .05). Hyperglycemia during normoinsulinemia did not affect A0.5 or phosphatase activity. In conclusion, (1) hyperinsulinemia for 2 1/2 hours increases glycogen synthase activity and activation by phosphatases independently on the glycemia; and (2) insulin receptor binding and basal and insulin-stimulated receptor kinase activity are not modified during short-term hyperinsulinemia and/or hyperglycemia.
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PMID:Effects of hyperinsulinemia and hyperglycemia on insulin receptor function and glycogen synthase activation in skeletal muscle of normal man. 190 47

The in vivo suppressive effect of glucose and insulin on plasma free fatty acid concentrations was investigated in obese subjects with (n = 6) and without (n = 6) Type 2 (non-insulin-dependent) diabetes mellitus during a 4h-hyperglycemic glucose clamp (about 11.2 mmol/l). Somatostatin was infused (250 micrograms/h) during the third h of glucose clamp to inhibit glucose-stimulated insulin secretion. Plasma insulin values were similar in the two groups at fasting and all throughout the study (F = 0.04; p = NS, two way analysis of variance), while the amount of glucose metabolized during the clamp was lower in diabetic subjects. Plasma free fatty acid concentrations, which were similar in the two groups at fasting, decreased during hyperglycemia and glucose-induced hyperinsulinemia (0-120 min; 180-240 min), and rose during hyperglycemia and somatostatin-inhibited insulin secretion (120-180 min). However, plasma free fatty acid concentrations were significantly higher in diabetic subjects all along the study period both in absolute terms (F = 11.4; p less than 0.0001) and when individual data were recalculated as percent of fasting value (F = 13.3; p less than 0.0001). Our data suggest that suppressibility of fasting plasma free fatty acids is lower in obese Type 2 diabetes in comparison with obese non-diabetic subjects.
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PMID:Glucose and insulin suppression of plasma free fatty acids in obese subjects with normal glucose tolerance or mild, newly diagnosed type 2 (non-insulin-dependent) diabetes. 196 30

The kinetics of insulin-mediated glucose uptake (IMGU) and non-insulin-mediated glucose uptake (NIMGU) in humans have not been well defined. We used the glucose-clamp technique to measure rates of whole-body and leg muscle glucose uptake in six healthy lean men during hyperinsulinemia (approximately 460 pM) to study IMGU and during somatostatin-induced insulinopenia to study NIMGU at four glucose levels (4.5, 9, 12, and 21 mM). To measure leg glucose uptake, the femoral artery and vein were catheterized, and blood flow was measured by thermodilution (leg glucose uptake = arteriovenous glucose difference [A-VG] x blood flow). With this approach, we found that, during hyperinsulinemia, both whole-body and leg glucose uptake increased in a curvilinear fashion at every glucose level, the highest glucose uptake values obtained being 139 +/- 17 mumol.kg-1.min-1 and 3656 +/- 931 mumol.min-1.leg-1, respectively. Leg blood flow increased twofold from 6.0 +/- 1.7 to 11.7 +/- 3.1 dl/min (P less than 0.01) over the range of glucose and was correlated with whole-body glucose uptake (r = 0.55, P less than 0.005). Leg muscle glucose extraction, independent of changes in blood flow, which is reflected by the A-VG, saturated over the range of glucose (1.28 +/- 0.12, 2.22 +/- 0.30, 2.92 +/- 0.42, 3.02 +/- 0.41 mM, NS between last 2 values) with a half-maximal effective glucose concentration (EG50) of 5.3 +/- 0.4 mM.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Kinetics of insulin-mediated and non-insulin-mediated glucose uptake in humans. 197 73

Amino acids stimulate the release of glucagon and insulin. To assess the role of aminogenic hyperglucagonemia, we have studied, in healthy young males, the effects of basal (less than 100 pg/ml) and high (200-400 pg/ml) plasma glucagon concentrations on amino acid metabolism during intravenous infusion (0.5 g.h-1.4 h) of a mixture of 15 amino acids. Basal plasma glucagon concentrations were obtained by infusion of somatostatin (0.5 mg/h) plus glucagon (0.25 ng.kg-1.min-1) and high plasma glucagon concentrations by infusion of somatostatin plus glucagon (3.0 ng.kg-1.min-1) or by infusion of amino acids alone. All studies were performed under conditions of euglycemic (83-91 mg/dl) hyperinsulinemia (50-80 microU/ml). Hyperglucagonemia significantly increased 1) net amino acid transport from the extracellular into the intracellular space (by approximately 4%), 2) net degradation of amino acids entering the intracellular space (by approximately 40%), and 3) conversion of degraded amino acids into glucose from 0-10% (basal glucagon) to 70-100% (high glucagon). Hyperglucagonemia did not affect the amount of amino acids excreted in the urine (approximately 4%). We conclude that glucagon plays an important role in the disposition of amino acids by increasing their inward transport, their degradation, and their conversion into glucose.
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PMID:Role of glucagon in disposal of an amino acid load. 197 87

Free fatty acids are known to inhibit carbohydrate disposal and oxidation. This action may play an important role in the pathophysiology of insulin resistance and non-insulin-dependent diabetes mellitus. To investigate whether amino acids (AAs) have similar actions, we determined the effects of an intravenously infused mixture of 15 AAs on carbohydrate disposal during euglycemic-hyperinsulinemic clamps associated with either basal or high glucagon concentrations in healthy male volunteers. Plasma glucose concentration was clamped at approximately 4.7 mM (coefficient of variation 4.7%). Insulin infusion (7.18 pmol.kg-1.min-1) raised serum insulin concentrations from 36-50 pM to between 300 and 600 pM. AA infusions (0.5 g.kg-1.h-1.4 h) raised plasma alpha-amino N2 concentrations about five- to six-fold. Infusion of AAs, somatostatin (somatotropin release inhibitory factor, SRIF), and high-glucagon replacement (3.0 ng.kg-1.min-1) reduced the rate of exogenous glucose infusion needed to maintain euglycemia from 51.1 +/- 7.2 mumol.kg-1.min-1 (saline + SRIF + high glucagon) to 28.3 +/- 11.1 mumol.kg-1.min-1 and stimulated endogenous glucose production (from 0 to approximately 17 mumol.kg-1.min-1). Thus, glucose disposal (exogenous infusion plus endogenous production of glucose) remained essentially unchanged. During infusion of AAs + SRIF + basal glucagon replacement (0.25 ng.kg-1.min-1), endogenous glucose production remained completely suppressed, and the rates of exogenous glucose infusion did not change (compared with saline + SRIF + basal glucagon replacement). The data showed that 1) hyperaminoacidemia associated with hyperglucagonemia stimulated endogenous glucose production despite hyperinsulinemia, and 2) intravenous infusion of a mixture of 15 AAs had no inhibitory effect on insulin-stimulated total-body glucose disposal.
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PMID:Effects of amino acids on glucose disposal. 197 39

Hyperinsulinism accompanies the raised luteinising hormone (LH) concentrations in women with the polycystic ovary syndrome (PCOS). Somatostatin inhibits insulin and LH secretion in healthy adults, so the effect of treatment with a long-acting somatostatin analogue ('Sandostatin') on gonadotropin and androgen secretion in PCOS was investigated. LH pulsatility, androgen concentrations, and hormonal responses to an oral glucose load and to administration of a GnRH agonist (buserelin) were measured before and after 7 days' treatment with sandostatin 100 micrograms subcutaneously twice a day in 10 amenorrhoeic women with classic features of PCOS. Sandostatin significantly reduced integrated LH concentrations and LH pulse amplitudes, oestradiol, testosterone, and androstenedione concentrations, and LH responses to buserelin; it also suppressed insulin and C-peptide responses to an oral glucose load. Thus sandostatin inhibits pituitary and ovarian hormonal responses in part by a direct influence on pituitary activity, and the possibility of an indirect effect mediated by changes in insulin concentrations requires investigation. These findings have implications for the treatment of infertility in women with PCOS.
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PMID:Inhibitory effect of sandostatin on secretion of luteinising hormone and ovarian steroids in polycystic ovary syndrome. 197 30


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