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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine whether synthetic somatostatin originally isolated from sheep hypothalamus can inhibit hormone secretion in the same species, we measured plasma levels of GH, insulin, glucagon, and glucose of normal sheep under a variety of experimental conditions in the presence and absence of somatostatin infusion. An oral dose of 2.5 mg./kg. 3,5-dimethypyrazole increase plasma GH from 10.9 to 376.9 ng. per milliliter, which was suppressed by 50 per cent and 80 per cent with 0.5 and 1 mg. synthetic cyclic somatostatin, respectively. Linear somatostatin (0.5 mg.) was without effect in two animals tested. Propionate (0.5 mmole per kilogram) and arginine (10 gm.) induced a rise in plasma insulin and GH, and glucagon was effectively blocked by cyclic somatostatin (0.5 mg.). Similarly, somatostatin inhibited glucose, and glucagon provoked GH and insulin secretory responses without affecting glucose or FFA levels. Somatostatin had no effect on the disappearance of injected glucagon. Finally, addition of somatostatin to incubation media prevented PGE promoted GH release, and suppressed cyclic AMP accumulation, although to a lesser extent, in sheep anterior pituitary pieces. In view of the large amounts required to suppress stimulated hormone release and the general lack of specificity of somatostatin, it is suggested that this peptide may have a functional role only in the release of hormones of the pituitary, where it could occur in relatively high local concentrations. Its inhibition of extrapituitary hormone secretion may be purely a pharmacologic effect that, nevertheless, suggests an interference with a step common to the secretory process of hormones.
Diabetes 1975 Sep
PMID:Studies on growth hormone secretion. VII. Effects of somatostatin on plasma GH, insulin, and glucagon in sheep. 16 76

Prostaglandin E(2) (PGE(2)) infusion in normal humans inhibited acute insulin responses to a glucose (5 g i.v.) pulse (response before PGE(2) = 593 +/- 104%; during PGE(2) = 312+/-55%; mean+/-SE, mean change 3-5 min insulin,% basal, P < 0.005). This effect was associated with a decrease in glucose disappearance rates (K(G) before PGE(2) = 0.73+/-0.07; during PGE(2) = 0.49+/-0.06%/min, P < 0.025). Acute insulin responses to arginine (2 g i.v.) were not affected by PGE(2) (response before PGE(2) = 592+/-164%; during PGE(2) = 590+/-118%; P = NS). Infusion of sodium salicylate (SS), an inhibitor of endogenous prostaglandin synthesis, augmented acute insulin responses to glucose in normals (response before SS = 313+/-62%; during SS = 660+/-86%; P < 0.001). In adult-onset diabetes with fasting hyperglycemia, SS restored absent acute insulin responses to glucose (20 g i.v.) pulses (response before SS = 5+/-6%; during SS = 97+/-24%; P < 0.005). This was accompanied by a fourfold augmentation in second phase insulin secretion (second phase before SS = 1,696+/-430%; during SS = 5,176+/-682%; change 10-60 min insulin, muU/ml.min,% basal, P < 0.001) and by acceleration of glucose disappearance rates (K(G) before SS = 0.56+/-0.06; during SS = 1.02+/-0.17%/min, P < 0.005). These findings uniquely demonstrate that (a) PGE(2) inhibits glucose-induced acute insulin responses and decreases glucose disposal in nondiabetic humans and (b) SS restores acute insulin responses, augments second phase insulin secretion, and accelerates glucose disposal in hyperglycemic, adultonset diabetics. It is hypothesized that endogenous PGE synthesis may play a role in defective insulin secretion and glucose intolerance in diabetes mellitus.
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PMID:A role for prostaglandin E in defective insulin secretion and carbohydrate intolerance in diabetes mellitus. 33 May 66

Urinary excretion of various renal prostaglandins was measured by radioimmunoassay and gas chromatography-mass spectrometry in children who had different degrees of metabolic control. Excretion in PGE2 in diabetic children was twice control values irrespective of the presence or absence of diabetic ketoacidosis (DKA). The urinary excretion of PGF2 alpha was significantly increased in diabetic children with ketoacidosis, but not when diabetes was well controlled. The excretion of 13, 14 dihydro-15-keto PGE2, the major metabolite of circulating PGE2, was increased in all diabetic children, and was most elevated in ketoacidosis when it averaged 10 times basal excretion. Urinary excretion of PGF2 alpha and of 6-keto-PGF1 alpha, the metabolite of PGI2, was approximately doubled in DKA compared with values from healthy subjects. Excretion of PGE2 was twice control values in children with stable diabetes, whereas the equivalent value for TXB2, the metabolite of the active vasoconstrictor TXA2, was reduced by approximately 50%. We suggest that the increased excretion of prostacyclin metabolite may result from a protective biological action on the kidney opposing other vasoconstrictor hormone activity. PGE2 appears not to be involved in this process. The highly elevated excretion of PGE2 metabolite may represent an activation of systemic PGE metabolism during DKA.
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PMID:Urinary prostaglandins in hyperglycaemic ketoacidosis of type I diabetes mellitus. 211 82

Platelet prostaglandin (PG) E and plasma PGF2 alpha concentrations were measured by radioimmunoassay methods and compared in non-pregnant and pregnant, normal and diabetic subjects. The blood samples were obtained in the follicular phase in the non-pregnant women and in the third trimester and after delivery in the pregnant women. The immunoreactive platelet PGE (IRPGE) levels were significantly higher in the pregnant diabetic women than in the normal non-pregnant and pregnant women and diabetic non-pregnant women. The immunoreactive plasma PGF2 alpha (IRPGF2 alpha) concentrations were significantly higher in the non-pregnant diabetic women than in the normal non-pregnant and pregnant women. During pregnancy, the plasma IRPGF2 alpha were further increased significantly in the diabetic subjects compared to the non-pregnant diabetics. Both the platelet IRPGE and plasma IRPGF2 alpha concentrations were higher in the pregnant diabetic subjects with retinopathy than in those without retinopathy. These findings suggest that pregnancy and diabetes influence the synthesis of PGE and PGF2 alpha in the platelets and plasma, respectively. The increased production of these prostaglandins are possible exacerbating factors of diabetic retinopathy during pregnancy.
Diabetes Res 1990 May
PMID:Elevation of immunoreactive platelet prostaglandin E and plasma prostaglandin F2 alpha in diabetic pregnancy. 213 65

The effect of E-series prostaglandins (PGE) on hormone-stimulated glycogenolysis was studied in isolated rat hepatocytes. As previously reported, the physiologically active analogue 16,16-dimethyl-PGE2 inhibited glucagon-stimulated glycogenolysis. This effect could be reproduced by repetitive addition of PGE2 to compensate for PGE2 catabolism. In contrast, glycogenolysis stimulated by N6,O2'-dibutyryladenosine-3',5'-cyclic monophosphate (dibutyryl-cAMP) was unaffected by either PGE2 or 16,16-dimethyl-PGE2 (rate of glycogenolysis with 0.34 microM dibutyryl-cAMP plus 1.7 microM 16,16-dimethyl-PGE2 = 99 +/- 6% of rate with 0.34 microM dibutyryl-cAMP alone; mean +/- SEM, N = 5). Similarly, glycogenolysis stimulated by 8-bromoadenosine-3',5'-cyclic monophosphate was not inhibited by PGE2 or 16,16-dimethyl-PGE2. Epinephrine-stimulated glycogenolysis was inhibited by 16,16-dimethyl-PGE2 in a dose-dependent manner. PGE inhibited the cAMP-independent stimulation of glycogenolysis resulting from phenylephrine or angiotensin II exposure (rate of glycogenolysis with 8 microM phenylephrine + 1.7 microM 16,16-dimethyl-PGE2 = 65 +/- 10% of rate with 8 microM phenylephrine alone, N = 4, P less than 0.05; 4.9 microM angiotensin II + 1.7 microM 16,16-dimethyl-PGE2 = 75 +/- 7% of rate with 4.9 microM angiotensin II alone, N = 4, P less than 0.05). Glycogenolysis stimulated by the calcium ionophore A23187 was also inhibited by PGE (rate of glycogenolysis with 0.55 micrograms/ml A23187 + 1.7 microM 16,16-dimethyl-PGE2 = 83 +/- 5% of rate with 0.55 micrograms/ml A23187 alone, N = 7, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1985 Mar
PMID:Effect of E-series prostaglandins on cyclic AMP-dependent and -independent hormone-stimulated glycogenolysis in hepatocytes. 298 82

The islets of Langerhans have the enzymatic equipment permitting the synthesis of the metabolites of arachidonic acid: cyclo-oxygenase and lipo-oxygenase. Numerous studies have shown that cyclo-oxygenase derivatives, mainly PGE2, reduce the insulin response to glucose whereas lipo-oxygenase derivatives, mainly 15-HPETE, stimulate insulin secretion. So, for instance, drugs that increase prostaglandins synthesis as colchicine or furosemide inhibit insulin secretion while non steroid anti-inflammator drugs, mainly salicylates, which inhibit cyclo-oxygenase, enhance the insulin response to various stimuli. In type-2 (non insulin-dependent) diabetes, an increased sensitivity to endogenous prostaglandins has been proposed as a possible cause for the insulin secretion defect which characterizes this disease. Play in favor of this hypothesis the fact that the administration of PGE inhibits the insulin response to arginine in type-2 diabetics but not in normal subject and the fact that the administration of salicylates could improve the insulin response to glucose in some of these patients.
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PMID:[Prostaglandins, insulin secretion and diabetes mellitus]. 307 92

Insulin therapy was withdrawn from 15 well-controlled type I diabetic subjects for no longer than 18 h to examine the sequence with which 13,14-dihydro-15-keto-PGE2 (PGE-m), glucagon, norepinephrine, and epinephrine increased in circulating blood in diabetic subjects becoming ketoacidotic. Fourteen of 15 patients had increments in PGE-m; 12/12, 12/15, and 13/15 had increments in glucagon, norepinephrine, and epinephrine, respectively. Six of the 15 patients developed mild diabetic ketoacidosis (DKA) by 12-18 h; all had nonmeasurable C-peptide levels. This DKA group had significantly greater increments of PGE-m (835 +/- 130 versus 276 +/- 111 pg/ml, mean +/- SEM, P less than 0.01) but not glucagon, norepinephrine, or epinephrine compared with the 9 non-DKA patients. In the DKA group, there were significant PGE-m and glucagon increments in the circulation by 3 h, significant norepinephrine increments by 9 h, and epinephrine increments in 5/6 patients by 12 h (not statistically significant) of insulin withdrawal. These studies document that (1) PGE-m accumulates in the circulation during DKA, (2) PGE-m and glucagon increase before catecholamines, and (3) PGE-m, glucagon, and catecholamine levels promptly return to normal levels when insulin therapy is reinstituted. It is suggested that elevated PGE-m levels early in the onset of DKA may represent a host-defense mechanism.
Diabetes 1985 Aug
PMID:Prostaglandin E2 metabolite levels during diabetic ketoacidosis. 392 65

Prostaglandins of the E series are implicated as regulators of glucose homeostasis because of their effects on glucose production and secretion of insulin and glucagon. PGE is postulated to play a role in the pathophysiology of insulin secretion in adult-onset (Type II) diabetes mellitus. Evidence supporting this hypothesis includes the demonstration that PGE inhibits glucose-induced acute insulin responses in normal humans. Moreover, drugs that inhibit synthesis of PGE improve abnormal insulin secretion in human subjects with Type II diabetes mellitus.
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PMID:Prostaglandins, glucose homeostasis, and diabetes mellitus. 634 49

Contractile responses to norepinephrine of the vas deferens isolated from normal and diabetic rats as well as tissue radio-conversion of exogenous arachidonic acid, were studied. Vasa deferentia from rats with acute streptozotocin-induced diabetes showed hypersensitivity to exogenous norepinephrine (NE). This increased contractile response was associated with the interaction of the agonist with alpha adrenoceptors. Inhibitors of cyclooxygenase increased and inhibitors of lipoxygenase(s) abolished the enhanced response to NE of diabetic vas deferens. Vasa deferentia from both normal and diabetic rats, converted (1-14C)-arachidonic acid (AA) into PGF, PGE, PGD and thromboxane (TX) B2, but the % of AA metabolites formed was significantly higher in the diabetic than in the normal condition. Moreover, the predominant prostanoid generated by tissue preparations from diabetic animals was PGD2. Taken together the present experimental findings indicate that preparations from rats with acute streptozotocin-induced diabetes have an augmented reactivity towards NE, which appeared associated with changes in metabolites of AA generated via cyclooxygenase and lipoxygenase catalized pathways.
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PMID:Hypersensitivity to norepinephrine in vasa deferentia from diabetic rats. Possible participation of metabolic products of arachidonic acid. 643 31

The present study is aimed at investigating the effect of acute and chronic colchicine administration on insulin secretion in humans. Acute insulin response to glucose (0.33 g/kg) was significantly decreased by colchicine (3 mg i.v.). In fact, this response (mean change 2-10 min insulin) was 44 +/- 8 microunits/ml before and 32 +/- 6 microunits/ml after colchicine administration (P less than 0.01). As a consequence of this, glucose disappearance rates were reduced (P less than 0.05). Infusion of lysine acetylsalicylate (LAS), an inhibitor of endogenous PG synthesis, completely reversed the inhibitory effect of colchicine upon insulin secretion and also augmented acute insulin response to glucose (response before colchicine + LAS = 45 +/- 8 microunits/ml; response after colchicine + LAS = 51 +/- 9 microunits/ml, P less than 0.05). This effect was associated with an increase in glucose disappearance rates (P less than 0.05). The 10-day treatment with colchicine (2 mg daily) caused a significant suppression of insulin secretion induced by oral glucose (100 g) and significantly increased the plasma glucose concentrations following the test (P less than 0.05). These findings demonstrate that (1) both acute and chronic colchicine administration inhibit glucose-induced insulin secretion and deteriorate glucose tolerance in humans, and (2) LAS completely reverses these negative effects of colchicine. An increased synthesis of endogenous PGE, which are known to inhibit insulin secretion in humans, might account for the inhibiting effect of colchicine on insulin secretion.
Diabetes 1981 Dec
PMID:Colchicine and insulin secretion in man. 679 45


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