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)

The effects of somatostatin plus intraportal insulin and glucagon replacement (pancreatic clamp) on carbohydrate metabolism were studied in conscious dogs fasted for 7 days so that gluconeogenesis was a major contributor to total glucose production. By use of [3-3H]glucose, glucose production (Ra) and utilization (Rd) and glucose clearance were assessed before and after implementation of the pancreatic clamp. After an initial control period, somatostatin (0.8 microgram . kg-1 . min-1) was infused with intraportal replacement amounts of glucagon (0.42 ng . kg-1 . min-1) and insulin. The insulin infusion rate was varied to maintain euglycemia and then kept constant (68 +/- 16 microU . kg-1 . min-1) for 250 min. Plasma glucagon was similar (84 +/- 14 and 89 +/- 19 pg/ml) before and during somatostatin infusion, while plasma insulin was lower (9.3 +/- 0.9 and 6.6 +/- 0.5 microU/ml, P less than 0.05). Plasma glucose levels remained similar (89 +/- 2 and 96 +/- 9 mg/dl), while Ra and Rd and the ratio of glucose clearance to plasma insulin were significantly (P less than 0.05) increased (from 2.18 +/- 0.12 to 3.21 +/- 0.35 and 2.30 +/- 0.09 to 3.26 +/- 0.38 mg . kg-1 . min-1, and 0.30 +/- 0.03 to 0.59 +/- 0.11, respectively). Net hepatic lactate uptake and [14C]alanine plus [14C]lactate conversion to [14C]glucose increased (P greater than 0.05) (from 9.32 +/- 0.47 to 16.54 +/- 2.97 mumol . kg-1 . min-1 and 100 to 263 +/- 37%, respectively). In conclusion, somatostatin alters glucose clearance in 7-day fasted dogs, resulting in changes in several indices of carbohydrate metabolism.
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PMID:Effect of somatostatin on glucose homeostasis in conscious long-fasted dogs. 288 63

Isolated hepatocyte studies demonstrated that leucine can be a precursor of ketone bodies. In this study we examine the relative contribution of leucine to hepatic ketogenesis in vivo. Three groups of conscious dogs with long-term indwelling catheters in the femoral artery, hepatic vein, and portal vein were studied. Group I (n = 3) animals were fasted overnight for 24 hours, and those in groups II and III (n = 4, each) were fasted for 62 to 68 hours (designated 3-day fast). Groups I and III received intravenous saline solution (0.9%) and served as controls. In group II selective acute insulin deficiency (SAID) was induced by a peripheral intravenous somatostatin (SRIF) infusion and intraportal glucagon (0.55 ng/body weight/min). Net hepatic production (NHP) of ketone bodies (kb) and leucine (leu) was measured by the arteriovenous difference technique. Hepatic conversion of leucine to ketone bodies was measured by continuous infusion of L-U-[14C]-leucine and by determination of the appearance of [14C]-ketone bodies across the liver. In the group fasted overnight NHPleu was 0.02 +/- 0.01 mumol/kg/min, a value not different from zero. NHPkb was 3.1 +/- 0.1 mumol/kg/min and hepatic conversion of leucine to ketone bodies accounted for 3.5% of NHPkb. Insulin deficiency after 3 day's fasting resulted in a near 70% increase in NHPleu (from basal values of 0.31 +/- 0.1 mumol/kg/min to 0.52 +/- 0.06 mumol/kg/min during SAID, p less than 0.01). NHPkb increased from 11.0 +/- 1.0 to 15.5 mumol/kg/min (p less than 0.05). The rate of leucine conversion to ketone bodies (L-C) increased from 1.1 +/- 0.25 to 2.4 +/- 0.3 mumol/kg/min (p less than 0.01) with SAID. We conclude that as the dog progresses to fasting, the contribution of leucine carbon to hepatic production of ketone bodies increases from 3.5% to 10% (p less than 0.01), and this value increases to 15% (p less than 0.01 versus groups I and II) after SAID. Furthermore, the amount of leucine carbon taken up by the liver was not sufficient to account for all [14C]-labeled leucine to ketone bodies. The data suggest that the leucine carbon converted to ketone bodies must have been derived from intrahepatic protein sources of possibly from the keto acids of leucine, which are derived by the breakdown of leucine at distant sites, such as skeletal muscle or adipose tissue.
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PMID:The role of leucine in hepatic ketogenesis. 289 77

Paired micropuncture experiments were carried out in plasma-replete volume-expanded rats to examine the acute effects of 1-desamino-8-D-arginine vasopressin (dDAVP) on urinary acidification and tubular handling of bicarbonate and chloride. No effect was detected on the fractional absorption of water, total CO2, and chloride at end-proximal and early distal sites of superficial nephrons in intact animals; dDAVP, however, inhibited the fractional absorption of total CO2 in Henle's loop while stimulating that of chloride in thyroparathyroidectomized (TPTX) somatostatin-infused rats. In the distal tubule accessible to micropuncture, net total CO2 secretion was observed during hypotonic volume expansion, which reversed to net total CO2 absorption during dDAVP infusion in intact Wistar rats. Marked stimulation of urinary acidification occurred in all animals as attested by a fall in urine pH and bicarbonate excretion. Net acid excretion almost doubled in intact rats. We conclude that (a) antidiuretic hormone (ADH) inhibits fractional bicarbonate absorption in the thick ascending limb while stimulating that of chloride at least in TPTX somatostatin-infused rats, and (b) ADH stimulates proton secretion (or inhibits bicarbonate secretion) in the distal tubule and cortical collecting ducts, which leads to enhanced urinary acidification.
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PMID:Effects of antidiuretic hormone on urinary acidification and on tubular handling of bicarbonate in the rat. 362 81

The aim of this study was to determine whether somatostatin had any effect on basal jejunal water and electrolyte fluxes, and whether it would inhibit glucagon-stimulated jejunal secretion in the conscious dog. Experiments were performed in 3 dogs with established jejunal fistulas by using the triple-lumen gut perfusion technique. Net water and electrolyte fluxes were measured during intravenous infusions of 150 mM NaCl, glucagon (30 micrograms . kg-1 . h-1), somatostatin (4 micrograms . kg-12 . h-1), and somatostatin plus glucagon. Results showed that glucagon stimulated jejunal water and electrolyte secretion (6 studies). This effect could be completely blocked by somatostatin infused before and with the glucagon (6 studies). In addition, established glucagon-stimulated secretion could be reversed to absorption by addition of somatostatin (6 studies). Somatostatin alone produced no change in net jejunal water and electrolyte fluxes.
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PMID:Somatostatin inhibition of glucagon-stimulated jejunal secretion in the dog. 611 13

The present study was designed to investigate the mechanisms by which insulin regulates the disposal of an intravenous glucose load in man. A combined tracer-hepatic vein catheter technique was used to quantitate directly the components of net splanchnic glucose balance (NSGB), i.e., splanchnic glucose uptake and hepatic glucose output, and peripheral (extrasplanchnic) glucose uptake. Four different protocols were performed: (a) intravenous infusion of glucose alone (6.5 mg kg(-1) min(-1)) for 90 min (control group); (b) glucose plus somatostatin (0.6 mg/h) and glucagon (0.8 ng kg(-1) min(-1); (c) glucose plus somatostatin, glucagon, and insulin (0.15 mU kg(-1) min(-1)); and (d) glucose plus somatostatin, glucagon, and insulin (0.4 m U kg(-1) min(-1)). In groups 2-4, arterial blood glucose was raised to comparable levels to those of controls ( approximately 170 mg/dl) by a variable glucose infusion. In the control group, plasma insulin levels reached 40 muU/ml at 90 min. NSGB switched from a net output of 1.71+/-0.13 to a net uptake of 1.5-1.6 mg kg(-1) min(-1) due to a 90-95% suppression of hepatic glucose output (P < 0.01) and a 105-130% elevation of splanchnic glucose uptake (from 0.78+/-0.13 to 1.6-1.8 mg kg(-1) min(-1); P < 0.01). Peripheral glucose uptake rose by 150-160% (P < 0.01). In group 2, plasma insulin fell to <5 muU/ml. Net splanchnic glucose output initially rose twofold but later returned to basal values. This response was entirely accounted for by similar changes in hepatic glucose output since splanchnic glucose uptake remained totally unchanged in spite of hyperglycemia. In contrast, peripheral glucose uptake rose consistently by 100% (P < 0.01) despite insulin deficiency. In an additional group of experiments, glucose metabolism by the forearm muscle tissue was quantitated during identical conditions to those of group 2 (hyperglycemia plus insulin deficiency). Both the arterial-deep venous blood glucose difference and forearm glucose uptake increased markedly by 300-400% (P < 0.05 - <0.01). In group 3, plasma insulin was maintained at near-basal, peripheral levels (12-14 muU/ml). Hepatic glucose output decreased slightly by 35-40% (P < 0.05) while splanchnic glucose uptake remained unchanged. Consequently, the net glucose overproduction seen in group 2 was totally prevented although NSGB still remained as a net output. In group 4, peripheral insulin levels were similar to those of the control group (35-40 muU/ml). The suppression of hepatic glucose output was more pronounced (60-65%) and splanchnic glucose uptake rose consistently by 65% (P < 0.01). Consequently, NSGB did not remain as a net output but eventually switched to a small uptake (0.3 mg kg(-1) min(-1)). Peripheral glucose uptake rose to the same extent as in controls. IT IS CONCLUDED THAT: (a) the suppressive effect of hyperglycemia on hepatic glucose output is strictly dependent on the degree of hepatic insulinization; (b) insulin plays an essential role in promoting splanchnic glucose uptake after an intravenous glucose load whereas hyperglycemia per se is totally unable to activate this process; (c) peripheral glucose uptake is markedly stimulated by hyperglycemia even in the face of insulin deficiency. Direct evidence also demonstrates that the skeletal muscle is involved in this response. Our data, thus, indicate that insulin rather than hyperglycemia regulates splanchnic glucose disposal in man. On the other hand, hyperglycemia per se appears to be an important regulator of glucose disposal by peripheral tissues.
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PMID:Differential effects of insulin on splanchnic and peripheral glucose disposal after an intravenous glucose load in man. 612 24

To study the effect of insulin on leucine kinetics, three groups of conscious dogs were studied after an overnight fast (16-18 h). One, saline-infused group (n = 5), served as control. The other two groups were infused with somatostatin and constant replacement amount of glucagon; one group (n = 6) received no insulin replacement, to produce acute insulin deficiency, and the other (n = 6) was constantly replaced with 600 muU/kg per min insulin, to produce twice basal hyperinsulinemia. Hepatic and extrahepatic splanchnic (gut) balance of leucine and alpha-ketoisocaproate (KIC) were calculated using the arteriovenous difference technique. l,4,5,[(3)H]Leucine was used to measure the rates (micromoles per kilogram per minute) of appearance (Ra) and disappearance (Rd), and clearance (Cl) of plasma leucine (milliliters per kilogram per minute). Saline infusion for 7 h resulted in isotopic steady state, where Ra and Rd were equal (3.2+/-0.2 mumol/kg per min). Acute insulin withdrawal of 4-h duration caused the plasma leucine to increase by 40% (P < 0.005). This change was caused by a decrease in the outflow of leucine (Cl) from the plasma, since Ra did not change. The net hepatic release of the amino acid (0.24+/-0.03 mumol/kg per min) did not change significantly; the arterio-deep femoral venous differences of leucine (-10+/-1 mumol/liter) and KIC (-12+/-2 mumol/liter) did not change significantly indicating net release of the amino and ketoacids across the hindlimb. Selective twice basal hyperinsulinemia resulted in a 36% drop in plasma leucine (from control levels of 128+/-8 to 82+/-7 mumol/liter, P < 0.005) within 4 h. This was accompanied by a 15% reduction in Ra and a 56% rise in clearance (P < 0.001, both). Net hepatic leucine production and net release of leucine and KIC across the hindlimb fell markedly. These studies indicate that physiologic changes in circulating insulin levels result in a differential dose-dependent effect on total body leucine metabolism in the intact animal. Acute insulin withdrawal exerts no effect on leucine rate of appearance, while at twice basal levels, insulin inhibited leucine rate of appearance and stimulated its rate of disappearance.
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PMID:Role of insulin in the regulation of leucine kinetics in the conscious dog. 612 47

Arterial (A) and renal venous (RV) concentrations and net splanchnic exchange of glucose, fructose, lactate, pyruvate, glycerol, and alanine were studied in the basal state and during a 135-min intravenous infusion of fructose at 2 mmol/min in healthy subjects after a 60-h fast. After 45 min of the fructose infusion, somatostatin (9 microgram/min) was infused for 60 min to induce hypoglucagonemia. Fructose infusion resulted in a net uptake of this hexose by the kidney as well as the splanchnic bed. Estimated renal uptake of fructose could account for the disposal of 20% of the administered fructose load while splanchnic uptake accounted for 38%. The fructose infusion resulted in a rise in blood glucose of 0.9 mmol/L, a 35% increase in net glucose output from the splanchnic bed, and a consistent net output of glucose from the kidney (A-RV = -0.17 +/- 0.05 mmol/L as compared with 0 +/- 0.03 in the basal state, P less than 0.02). Net glucose release from the kidney could account for 55% of the net renal uptake of fructose. The fructose infusion also resulted in a marked change in renal lactate balance from a net uptake in the basal state (A - RV = 0.05 +/- 0.01 mmol/L) to a net output during fructose administration (A - RV = -0.10 +/- 0.04). Administration of somatostatin resulted in a fall in arterial glucagon levels and a 35% decrease in splanchnic glucose output but failed to alter the arterial-renal venous difference for glucose observed during the fructose infusion. We conclude that in 60-h fasted man: (a) intravenous infusion of fructose results in a net uptake of this hexose by the kidney as well as the liver, (b) this uptake is accompanied by stimulation of renal as well as hepatic glucose production and renal production of lactate, and (c) hypoglucagonemia inhibits splanchnic but not renal glucose output during fructose infusion. These data indicate that the kidney is an important site of fructose disposal and that glucose and lactate are end products of renal fructose metabolism.
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PMID:Role of the kidney in the metabolism of fructose in 60-hour fasted humans. 613 22

The aim of the present study was to investigate the influence of hepatic glycogen depletion and increased lipolysis on the response of splanchnic glucose output and ketogenesis to combined glucagon and insulin deficiency in normal man. Healthy subjects were studied after a 60-h fast and compared with a control group studied after an overnight fast. Net splanchnic exchange of glucose, gluconeogenic precursors, free fatty acids (FFA) and ketone acids were measured in the basal state and during intravenous infusion of somatostatin (9 micrograms/min) for 90-140 min (overnight fasted subjects) or for 5 h (60-h fasted subjects). During the infusion of somatostatin, euglycemia was maintained by a variable intravenous infusion of glucose. Prior to somatostatin infusion, after an overnight (12-14 h) fast, splanchnic uptake of glucose precursors (alanine, lactate, pyruvate, glycerol) could account for 26% of splanchnic glucose output (SGO) indicating primarily glycogenolysis. Somatostatin infusion resulted in a 50% reduction in both insulin and glucagon concentrations and a transient decline in SGO which returned to baseline values by 86 +/- 11 min at which point the glucose infusion was no longer necessary to maintain euglycemia. Arterial concentrations of FFA and beta-OH-butyrate and splanchnic beta-OH-butyrate production rose 2.5-fold, 6-fold and 7.5-fold, respectively, in response to somatostatin infusion. In the 60-h fasted state, basal SGO (0.29 +/- 0.03 mmol/min) was 60% lower than after an overnight fast and basal splanchnic uptake of glucose precursors could account for 85% of SGO, indicating primarily gluconeogenesis. Somatostatin administration suppressed the arterial glucagon and insulin concentrations to values comparable to those observed during the infusion in the overnight fasted state. SGO fell promptly in response to the somatostatin infusion and in contrast to the overnight fasted state, remained inhibited by 50-100% for 5 h. Infusion of glucose was consequently necessary to maintain euglycemia throughout the 5-h infusion of somatostatin. Splanchnic uptake of gluconeogenic precursors was unchanged during somatostatin despite the sustained suppression of SGO. Basal arterial concentration and splanchnic exchange of beta-OH-butyrate were respectively 22-fold and 6- to 7-fold elevated and basal FFA concentration was 70% increased as compared to the corresponding values in the overnight fasted state.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of basal glucagon levels in the regulation of splanchnic glucose output and ketogenesis in insulin-deficient humans. 614 27

Teleost fish osmoregulation is largely the result of integrated transport activities of the gill, gut and renal system. The basic 'epithelial fabric' in each of these tissues is adapted to provide the appropriate transport mechanisms depending upon whether the fish is in fresh water or sea water. Net NaCl transport by the branchial epithelium reverses direction when euryhaline species migrate between the two media, providing a useful focus in experiments designed to elucidate mechanisms of differentiation and integration of transport function. Isolated opercular membranes and skins from certain seawater-adapted species are good models to study branchial salt extrusion mechanisms. These heterogeneous tissues generate short-circuit currents equal to net chloride secretion. The vibrating probe technique has allowed localization of all current and almost all conductance to the apical crypt of chloride cells. Area-specific surface current and conductance of chloride cells are 18 mA cm-2 and 580 mS cm-2 (1.7 omega cm2), ranking them as one of the most actively transporting and conductive cells known. There is no net sodium transport under short-circuit conditions but the chloride secretion process is sodium-dependent and ouabain and 'loop'-diuretic sensitive. Sodium fluxes through chloride cells are large (PNa = 5.2 X 10(-4) cms-1) nd appear passive and rate-limited by a single barrier. A link may exist between the active transport and leak pathways since sodium fluxes always account for 50% of chloride cell conductance. The sodium pathway is probably the chloride cell-accessory cell tight junction, although this is still unresolved. Chloride secretion can be rapidly modulated by several hormones, including catecholamines, somatostatin, glucagon, vasoactive intestinal polypeptide and urotensins I and II. Regulation by these hormones may be by rapid alterations of cellular cAMP levels. Differentiation of chloride cells and chloride secretion may be controlled by cortisol and prolactin. Cortisol stimulates chloride cell proliferation and differentiation and appears to interact with NaCl to initiate salt secretion. Prolactin appears to cause chloride cell dedifferentiation by reducing both the active-transport and leak pathways proportionately.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Chloride cells and the hormonal control of teleost fish osmoregulation. 636 Dec 7

The aim of this study was to assess the importance of epinephrine as a gluconeogenic hormone in the conscious 18-h-fasted dog. Glucose production ([3H]glucose turnover) and gluconeogenesis [( 14C]alanine conversion to [14C]glucose; and transhepatic gluconeogenic substrate balances) were assessed during epinephrine infusion (0.04 microgram X kg-1 X min-1). Insulin and glucagon were fixed at basal levels (13 +/- 1 microU/ml and 138 +/- 16 pg/ml, respectively) using a pancreatic clamp [somatostatin (0.8 microgram X kg-1 X min-1) plus intraportal insulin (233 microU X kg-1 X min-1) and glucagon (0.65 ng X kg-1 X min-1)]. Plasma epinephrine levels increased to 424 +/- 48 pg/ml. Glucose production increased rapidly (15 min) from 2.7 +/- 0.3 to 3.7 +/- 0.4 mg X kg-1 X min-1 (P less than 0.01) but then returned to base line (2 h). The plasma glucose level rose progressively from 115 +/- 16 to 160 +/- 16 mg/dl (P less than 0.01) at 3 h, whereas glucose clearance fell by 28% (P less than 0.05). Plasma alanine rose from 340 +/- 20 to 497 +/- 50 microM, and blood lactate increased from 640 +/- 135 to 1,910 +/- 241 microM. Net hepatic alanine and lactate uptake increased to maxima of 4.0 +/- 0.3 and 9.3 +/- 2.0 mumol X kg-1 X min-1, respectively. The conversion of alanine to glucose increased by a maximum of 163 +/- 56% (vs. 49 +/- 16% in controls not given epinephrine), whereas the efficiency with which the liver converted alanine to glucose rose by 84 +/- 27% (vs. 82 +/- 12% in controls not given epinephrine).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of epinephrine on glycogenolysis and gluconeogenesis in conscious overnight-fasted dogs. 638 Mar 3


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