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

Cardiomyopathy is a complication of human diabetes mellitus. The relationship of cardiac function to the beta-adrenergic receptor and catecholamine-stimulated adenylate cyclase activity was investigated in the streptozotocin-diabetic rat. beta-Adrenergic receptor number in cardiac membranes from diabetic rats was reduced. After 2 weeks of diabetes, the response of adenylate cyclase to isoproterenol stimulation was not altered. Cardiac contractile function assessed by the maximum rate of rise of left ventricular pressure (LV dP/dtmax) in an open-chest anesthetized rat was also unchanged from control at 2 weeks. However, after 4 weeks of diabetes, the sensitivity of adenylate cyclase to isoproterenol stimulation was depressed and abnormalities in cardiac contractility were noted, including a depressed response of LV dP/dtmax to graded isoproterenol infusion. These studies suggest that alterations in beta-adrenergic receptors and their coupling to adenylate cyclase may be important in the development of diabetic cardiomyopathy.
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PMID:beta-Adrenergic receptors, adenylate cyclase activity, and cardiac dysfunction in the diabetic rat. 258 Jan 53

When tested in insulin-deficient animal models of diabetes, islet activating protein (IAP) has been shown to increase the secretion of insulin and to improve glucose intolerance. The genetically obese fa/fa rat is an animal model of impaired oral glucose tolerance that does not have reduced insulin secretion. In this model IAP treatment increases basal insulin levels, resulting in lower basal glycemia. However, glucose tolerance following an oral glucose load was worsened by IAP. This was found to be due to an exaggerated stimulation of hepatic glucose production (HGP) following glucose, a defect that is already present in the absence of IAP. IAP has been reported to inhibit (by ADP ribosylation) the inhibitory regulatory protein (Ni) of adenylate cyclase. It is therefore suggested that the increased HGP following oral glucose in fa/fa rats either in the absence or in the presence of IAP treatment may result from a cAMP-mediated mechanism. A beta adrenergic activation or a stimulation of glucagon output could therefore be potential candidates responsible for glucose intolerance in obese fa/fa rats.
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PMID:The effects of islet activating protein on oral glucose tolerance in the genetically obese fa/fa rat. 265 21

1. The erectile response to the short-acting dopamine (DA) receptor agonist, apomorphine (Apo) HCl (0.25, 0.5, 0.75 and 1.0 mg sc), and placebo was evaluated in 28 impotent patients and penile circumference monitored using a mercury strain gauge and strip chart recording. 2. A full erection (increment in penile circumference greater than 2 cm and lasting at least one minute) occurred in 17 patients with Apo; no erection developed after placebo. An erection occurred in 6/8 patients with impaired glucose tolerance, 2/6 patients with diabetes mellitus and in both patients on lithium. 3. Nine patients who responded to Apo were treated in an open trial with bromocriptine; 6 reported improvement in potency. 4. Impairment in DA function may play a role in idiopathic impotence and in impotence associated with impaired glucose tolerance and diabetes mellitus. 5. An erectile response to Apo may predict therapeutic response to bromocriptine or other long acting dopaminergic agents. 6. Lithium, which inhibits DA-sensitive adenylate cyclase, does not prevent Apo-induced erections. This provides further support indicating that Apo induces erections by an effect on D2 receptors. 7. The yawning response to placebo and four doses of Apo HC1 (3.5, 5.0, 7.0, and 10.5 ug/kg sc) was evaluated in five normal men using a polygraphic technique. The yawning response was also assessed in normal young (less than 30 yrs; N = 16) and elderly (greater than 60 yrs; N = 12) volunteers. 8. Under experimental conditions of study, placebo induced spontaneous yawning. This was antagonized by 3.5 and 5.0 ug/kg Apo HC1 but increased by 7.0 ug/kg Apo HC1. These observations are compatible with the view that Apo HC1 in doses of 3.5-5.0 ug/kg stimulates presynaptic DA receptors whereas 7.0 ug/kg stimulates postsynaptic DA receptors. 9. Spontaneous and Apo-induced yawning were significantly decreased in the elderly which suggests that D2 receptor function declines with normal aging.
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PMID:Apomorphine: clinical studies on erectile impotence and yawning. 274 70

Since the mechanisms responsible for stimulation of kidney Na-K-ATPase during streptozotocin-induced diabetes are unknown, we studied the possible role(s) of kidney hyperfiltration and hypertrophy and of hyperaldosteronism on Na-K-ATPase induction. For this purpose, we studied the relationship between Na-K-ATPase activity in individual nephron segments and alterations of glomerular filtration rate during the early phase of diabetes. Within 2 days after streptozotocin administration, Na-K-ATPase activity markedly increased in the proximal convoluted tubule, medullary thick ascending limb and cortical and outer medullary collecting tubule, but not in the proximal straight tubule, cortical thick ascending limb and distal convoluted tubule. Streptozotocin administration also markedly enhanced the glomerular filtration rate but only after 4 days following initiation of treatment. Changes in Na-K-ATPase were specific since the activity of adenylate cyclase, another marker of basolateral membranes, was not altered. Finally, when animals were adrenalectomized prior to streptozotocin treatment, Na-K-ATPase stimulation was curtailed in the collecting tubule but not in more proximal segments. These results suggest that diabetes alters Na-K-ATPase activity in specific nephron segments independent of alterations of glomerular filtration rate and of kidney hypertrophy, and that the stimulation of collecting tubule Na-K-ATPase is secondary to hyperaldosteronism.
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PMID:Mechanism of increased tubular Na-K-ATPase during streptozotocin-induced diabetes. 281 17

Specific gastric inhibitory polypeptide (GIP) receptors were characterized in human benign insulinoma plasma membranes employing [mono-[125I]iodo-Tyr10]-GIP (125I-GIP) as the radioligand. GIP 1-42 inhibited 125I-GIP binding with an IC50 value of 10(-9) M. Scatchard analysis showed two classes of binding sites: a high-affinity site (Kd = 2.23 x 10(-10) M; Bmax = 24 fmol/mg protein) and a low-affinity site (Kd = 8.39 x 10(-9) M; Bmax = 118 fmol/mg protein). A synthetic replicate of human GIP 1-31 inhibited 125I-GIP binding with an IC50 value of 10(-8) M. The GIP binding sites of human insulinoma were coupled to adenylate cyclase stimulation. GIP 1-31 regulated the adenylate cyclase activity to the same extent as GIP 1-42. The concentrations of GIP required for maximal activity ranged from 10(-9) to 10(-8) M for either GIP 1-42 or GIP 1-31. The existence of functional GIP receptors in human insulinoma substantiates our recent reports demonstrating the presence of GIP binding sites in transplantable hamster insulinoma and indicates that GIP could exert a direct control of the beta-cell function in humans through a purely endocrine pathway.
Diabetes 1987 Nov
PMID:Evidence of functional gastric inhibitory polypeptide (GIP) receptors in human insulinoma. Binding of synthetic human GIP 1-31 and activation of adenylate cyclase. 282 18

The effect of sulfonylureas tolbutamide and glyburide on adenylate cyclase- and cAMP-dependent protein kinase (A-kinase) was examined in rat liver cytosol. Both tolbutamide and glyburide inhibited the A-kinase activity in a dose-dependent manner. Half-maximal inhibition was obtained at 10 mM with tolbutamide and at 0.2 mM with glyburide, indicating that glyburide was 50-fold as potent as tolbutamide. Neither tolbutamide nor glyburide affected [3H]cAMP binding to the protein kinase, but both inhibited the activity of catalytic units of the A-kinase. Lineweaver-Burk double-reciprocal plots revealed that the inhibitory effects of these drugs were noncompetitive with respect to the protein substrate histone, as well as to the phosphate-donor substrate ATP. Thus, tolbutamide and glyburide inhibited the A-kinase activity in rat liver cytosol, and it was suggested that, through the inhibition of A-kinase, the sulfonylureas would affect the carbohydrate metabolism in the liver. In fact, the relative potencies of these two drugs on A-kinase activity corresponded well with those of their reported antidiabetic effects.
Diabetes 1988 Jul
PMID:Effect of tolbutamide and glyburide on cAMP-dependent protein kinase activity in rat liver cytosol. 283 57

The number of beta-adrenergic receptors in cardiac myocytes isolated from rats made diabetic with streptozocin (STZ) for 10 wk was measured by use of a hydrophilic nonselective antagonist [3H]CGP 12177 and was found to decrease to 59% of the number in control rats (P less than .05), without any change in affinity. Similarly, using [125I]iodocyanopindolol as a ligand, we found a decrease in the beta-adrenergic-receptor number on cardiac plasma membrane isolated from the diabetic rats [29% decrease (P less than .05) at 1 wk, 50% (P less than .01) at 3 wk, and 49% (P less than .01) at 10 wk compared with control rats]. However, the serum triiodothyronine level that had been known to modulate the beta-adrenergic-receptor-adenylate cyclase system was decreased in the 1-wk-diabetic rats but not in the 10-wk-diabetic rats compared with each control group. Furthermore, there was no difference in urinary catecholamine excretion between diabetic and control groups. In the 10-wk-diabetic rats, the response of adenylate cyclase to isoproterenol was significantly defective (56% decrease compared with control rats; P less than .05), although both the basal and the forskolin-stimulated maximum adenylate cyclase activities and a half-maximum concentration of isoproterenol for the stimulation of adenylate cyclase were similar in control and diabetic rats. On the other hand, both cholera toxin-dependent and islet-activating protein-dependent [32P]NAD incorporations into cardiac plasma membrane were markedly increased in the diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1988 Sep
PMID:Deficiency of cardiac beta-adrenergic receptor in streptozocin-induced diabetic rats. 284 11

Zinc deficiency and altered myocardial adenylate cyclase activity commonly occur in diabetes. To determine whether the zinc intake of the animal can account for the altered beta-adrenergic receptor activity in the diabetic heart, we determined the beta-adrenergic receptor number and isoproterenol-, NaF- and forskolin-stimulated adenylate cyclase activity in diabetic and control rats maintained on low, normal and high zinc diets for 3 weeks. Scatchard analysis of [125I]iodocyanopindolol binding to control heart membrane preparations revealed a binding capacity of 17.3 +/- 1.3 fmol/mg protein with a Kd of 35 +/- 1.0 pmol/l. Neither the diabetic state nor the zinc status altered these binding parameters. The isoproterenol-stimulated adenylate cyclase activity was significantly lower in diabetic rats on low zinc diets compared with controls. The NaF- (65.1 +/- 5.4 vs 60.8 +/- 6.4 pmol cAMP.mg protein-1.min-1) and forskolin-stimulated adenylate cyclase activities (161 +/- 9.3 vs 154 +/- 21.2 pmol cAMP.mg protein-1. min-1) were not significantly altered in diabetic rats. Low dietary zinc intake compared with high zinc diet significantly increased NaF- and forskolin-stimulated adenylate cyclase activity both in diabetic rats and controls. The effect of dietary zinc content on isoproterenol-stimulated adenylate cyclase was significant in control rats only. Thus zinc intake appears to be an important determinant of cardiac adenylate cyclase activity level. Additional factors peculiar to the diabetic state are involved in the modulation of beta-adrenergic responsiveness of the diabetic heart.
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PMID:The role of zinc status in altered cardiac adenylate cyclase activity in diabetic rats. 284 90

The role of cytoplasmic activator of adenylate cyclase in rat lung metabolism was investigated. Mouse adrenal tumor (MAT) cells undergo differentiation in response to choleratoxin which acts through cyclic AMP. The activator of adenylate cyclase from rat lung also produced cyclic AMP in a disrupted MAT cell preparation. However, unlike choleratoxin, it did not induce MAT cell differentiation in whole cells. These results suggest impermeability of MAT cells, and possibly other cells, to the activator. Thus, means of altering activator activity in lung cytoplasm were sought, and changes in activator activity were related to lung glycogen. Adrenalectomy (ADX) in rats led to a reduction in activator activity that was accompanied by an elevation in lung glycogen. Dexamethasone treatment of adrenalectomized rats reversed both of these effects. Streptozotocin-induced diabetes in rats elevated activator activity and lowered lung glycogen. Insulin treatment of the diabetic rats restored activator activity to the normal control values. Preweaning of rats on day 16 instead of day 22 increased activator activity on the 19th day over the controls and there was a concomitant decrease in lung glycogen. Feeding the separated pups with homogenized milk restored glycogen and activator activity to the control values. These results indicate that activator activity in rat lung cytoplasm was dependent on the circulating levels of cortisol and insulin, and that there appeared to be an inverse relationship between activator activity and glycogen level in rat lungs.
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PMID:Relationship between the cytoplasmic activator of adenylate cyclase and glycogen metabolism in rat lung. 285 15

The effects of streptozotocin-induced diabetes on the retinal dopaminergic system have been examined in Long-Evans (pigmented) rats. Tyrosine hydroxylase activity was significantly decreased while dopamine-stimulated adenylate cyclase was increased in 2-month-diabetic rats. The observed increase in dopamine-stimulated adenylate cyclase activity in diabetic retinae may be related to neurotransmitter receptor changes because postreceptor activation of adenylate cyclase by guanylyl imidodiphosphate was not altered.
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PMID:Dopamine-stimulated adenylate cyclase and tyrosine hydroxylase in diabetic rat retina. 286 Sep 52


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