Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phosphorylation site stoichiometries were determined for skeletal muscle glycogen synthase purified from control, alloxan-diabetic, and epinephrine-treated rabbits. One method of analysis was direct determination of the total in vivo phosphate content of each site after reverse phase high performance liquid chromatography separation of a complete tryptic digest of the purified synthase. The second method of analysis, in vitro phosphorylation, was based on the premise that in vitro 32P incorporation into each site would be inversely related to the in vivo phosphate content of that site. Glycogen synthase from control rabbits had the following distribution of in vivo phosphate (mole of phosphate/mol of site): site 1a, 0.29 +/- 0.08; site 5, 0.62 +/- 0.07; site 3, 0.46 +/- 0.06; site 1b, 0.23 +/- 0.03; and site 2, 0.43 +/- 0.07. Synthase from diabetic rabbits had 2-fold elevations of in vivo phosphate contents of sites 2 and 3. Epinephrine resulted in increased phosphorylation in vivo of site 1b (2.0-fold), site 2 (2.0-fold), and site 3 (1.5-fold). The in vitro phosphorylation analysis showed decreased 32P incorporation in vitro (indicative of increased in vivo phosphorylation) as follows: epinephrine, site 1a, site 3, site 1b, site 2; diabetic, site 3, site 2. The effect of diabetes on the in vitro phosphorylation of sites 2 and 3 was reversed by insulin treatment. We conclude that the major effect of epinephrine, phosphorylation of sites 1a, 1b, and 2, is mediated by the activation of the cAMP-dependent kinase. The mechanisms accounting for the phosphorylation of site 3 in response to epinephrine and phosphorylation of sites 2 and 3 in the diabetic state are under investigation.
 ...
PMID:Effects of epinephrine, diabetes, and insulin on rabbit skeletal muscle glycogen synthase. Phosphorylation site occupancies. 632 4

Glucagon normally plays a primary role in promoting glucose recovery from insulin-induced hypoglycemia. Epinephrine compensates largely for deficient glucagon secretion. Glucose recovery from hypoglycemia fails to occur only in the absence of both glucagon and epinephrine. Perhaps as a relatively early feature of autonomic neuropathy, patients with insulin-dependent diabetes mellitus commonly have blunted or absent glucagon secretory responses to hypoglycemia. However, this deficient response is commonly compensated for by epinephrine and glucose recovery occurs. In some patients, progression of adrenergic neuropathy to the point of deficient epinephrine secretory responses to hypoglycemia, coupled with deficient glucagon responses, leads to frequent, severe, and prolonged hypoglycemia. Thus, these glucose counterregulatory systems are of critical importance to patients with insulin-dependent diabetes mellitus. The efficacy of glucose counterregulation in a given patient may determine the degree to which euglycemia can be achieved with aggressive insulin therapy in that patient.
Diabetes Care
PMID:Relevance of glucose counterregulatory systems to patients with diabetes: critical roles of glucagon and epinephrine. 634 Oct 18

Epinephrine causes a prompt increase in blood glucose concentration in the postabsorptive state. This effect is mediated by a transient increase in hepatic glucose production and an inhibition of glucose disposal by insulin-dependent tissues. Epinephrine augments hepatic glucose production by stimulating glycogenolysis and gluconeogenesis. Although its effect on glycogenolysis rapidly wanes, hyperglycemia continues because the effects of epinephrine on gluconeogenesis and glucose disposal persist. Epinephrine-induced hyperglycemia is markedly accentuated by concomitant elevations of glucagon and cortisol or in patients with diabetes. In both cases, the effect of epinephrine on hepatic glucose production is converted from a transient to a sustained response, thereby accounting for the exaggerated hyperglycemia. During glucose feeding, mild elevations of epinephrine that have little effect on fasting glucose levels cause marked glucose intolerance. This exquisite sensitivity to the diabetogenic effects of epinephrine is accounted for by its capacity to interfere with each of the components of the glucoregulatory response, i.e., stimulation of splanchnic and peripheral glucose uptake and suppression of hepatic glucose production. Our findings suggest that epinephrine is an important contributor to stress-induced hyperglycemia and the susceptibility of diabetics to the adverse metabolic effects of stress.
 ...
PMID:Effect of epinephrine on glucose metabolism in humans: contribution of the liver. 638 Mar 4

To be able to study the long-term effects of moderately enhanced catecholamine levels in rats, we developed subcutaneously implantable retard systems, granting a linear output of various agents throughout the test time. Adrenaline application leads to hyperglycemia without elevation of serum immune-reactive-insulin (IRI) during 20 h of uninterrupted adrenaline (A) action. This we call an A-induced diabetes like reaction. It could be completely abolished by simultaneous application of low phentolamine (Regitin) doses. Simultaneous application of propranolol (P) gradually diminished blood glucose levels from about 200 mg/dl after 6 h to 120 mg/dl after 20 h. Since here insulin levels are uniformly low, decline of blood glucose could not be due to enhanced insulin-action. The moderate hyperglycemia after 6 h isoprenaline (ISO)-treatment alone goes with a hyperinsulinemia at the same time. Obviously this hyperinsulinemia cannot cope with the increased blood glucose probably due to enhanced liver-glycogenolysis by intact alpha-action. Later on insulin--despite of beta-action on pancreas--declines strictly proportional with diminishing blood-glucose-levels. A comparison between the action of catecholamines and their blockers showed that alpha-blockers tend to diminish blood glucose levels by two independent ways, namely by the inhibitory action on pancreas and the inhibitory action on liver glycogenolysis.
 ...
PMID:Peculiar long-term effects of catecholamines and their blockers in rats on insulin, glucose and pancreas. 639 61

The response to vasoactive agents of microvessels of the rat was tested in vivo by direct microscopic observation of the exteriorized mesentery and assessment of cutaneous vascular permeability changes with Evans blue. The constrictor response to a standard amount of noradrenaline in mesenteric microvessels was fully antagonized by acetylcholine in normal, diabetic, adrenalectomized and diabetic-adrenalectomized rats. In contrast, the minimum doses of histamine or bradykinin, effective in normal or adrenalectomized animals, had to be increased about 20 fold to be active in diabetic or diabetic-adrenalectomized animals. Topical application of insulin to mesenteric microvessels of diabetic animals, in amounts not causing any increase in serum insulin levels, improved or restored the capacity of the animals to respond to histamine or bradykinin, acting as antagonists of the vasoconstrictor response to noradrenaline. Topical insulin, however, was ineffective in normal animals given 2-deoxyglucose, the acute effects of which result from cellular glucopaenia unrelated to insulin deficiency. Vascular permeability responses to intracutaneous histamine or bradykinin were decreased in animals pretreated with 2-deoxyglucose as much as in diabetic animals. Pretreatment of normal animals with indomethacin produced no effect on the responses of these animals to histamine or bradykinin, tested as antagonists of noradrenaline on mesenteric microvessels, or as vascular permeability-increasing factors in the skin. Pretreatment of normal animals with chloroquine, mepacrine or dexamethasone had no effect on the reactivity of mesenteric microvessels to histamine and bradykinin, acting as antagonists to noradrenaline. 7 It is suggested that vasoactive substances, endowed with permeability-increasing properties, evoke relaxation of microvessels through an insulin-dependent action on endothelial cells, unrelated to the release of arachidonic acid metabolites. This action would lead to increased vascular permeability, with opening of interendothelial junctions, and temporary changes in composition of extravascular fluid, which in turn, would provide the basis for vasodilatation. Diabetes mellitus apparently impairs such responses as a result of the accompanying cellular glucopaenia. Adrenal corticosteroids are not involved in the impaired responses.
 ...
PMID:Vascular reactivity in diabetes mellitus: possible role of insulin on the endothelial cell. 643 70

The 24-h excretion of free, conjugated and total fractions of dopa, dopamine, noradrenaline and adrenaline was studied in 32 patients with diabetes mellitus. Adrenaline and dopamine were established to be increased--dopa decreased and noradrenaline--not changed. An attempt is made to explain the hormonal changes on the base of the analysis of the so called synthetic and dissociative coefficients of catecholamines. A moderate reverse correlation of the changes with the age of the patients and duration of diabetes was established as well as lower values in the female-diabetics versus the male-diabetics. The hormonal deviations are associated with the disturbances in the carbohydrate metabolism, have a reactive character and are manifested in insulin-dependent type of diabetes.
 ...
PMID:[Excretion of free and bound catecholamines in the urine of diabetes mellitus patients]. 650 63

Autoantibodies to the adrenal cortex (AA) were sought by indirect immunofluorescence using unfixed human adrenal tissue in 1675 patients with insulin-dependent diabetes (IDD), 2032 relatives of patients with IDD, and 2543 normal subjects. The frequencies of AA were significantly greater in patients with IDD (1.8%) and their relatives (1.4%) than in normal subjects (0.6%; P less than 0.013). Women more frequently had AA than men (P less than 0.011). There were no differences in the frequencies of AA between caucasoid and black individuals in all three patient groups. Patients with AA had higher frequencies of thyroid microsomal and gastric parietal cell autoantibodies than age-, sex-, and race-matched normal subjects (P less than 0.01). Adrenal function was studied in 30 asymptomatic patients (13 with AA, including 5 with IDD, and 17 subjects with no AA, including 8 with IDD). The mean plasma levels of ACTH at 0600 and 2000 h were significantly higher in those with AA than in matched subjects with no AA (P less than 0.01). The mean PRA levels (both recumbent and upright) were also significantly higher in those with AA than in subjects without AA (P less than 0.01). However, serum cortisol and aldosterone concentrations or 24-h urinary cortisol and aldosterone excretion were no different between the groups. These patients, therefore, appear to have compensated adrenal hypofunction, with the compensation maintained by increased ACTH and renin secretion. Whether these patients will remain in this compensated state of adrenal dysfunction or whether they will develop overt adrenal insufficiency requires longer follow-up.
 ...
PMID:Adrenal dysfunction in asymptomatic patients with adrenocortical autoantibodies. 672 13

To characterize the pancreatic islet cell responses to adrenergic stimulation, membrane potentials have been recorded from isolated, perifused mouse islets of Langerhans exposed to a steady glucose level of 200 mg/dl. Various doses of epinephrine HCl from 5 to 10,000 nM have been applied for 10--15-min test periods separated by 10--15-min control periods. Epinephrine produced a dose-dependent suppression of glucose-induced membrane electrical activity. Adding epinephrine (50--100 nM) reduced the plateau fraction (the fraction of each plateau/silent phase cycle spent in the plateau phase) from 0.41 +/- 0.03 (X +/- SEM, N = 13) to 0.28 +/- 0.08 (N = 5, P = 0.05) and more markedly reduced the plateau frequency from 2.56 +/- 0.32 (N = 13) to 0.80 +/- 0.23 min-1 (N = 5, P less than 0.02). Adding 10- and 100-fold higher concentrations of epinephrine had little additional effect. There was no effect of epinephrine on the membrane potential levels of the plateau and silent phase after a new steady state was achieved and no effect on the amplitude and waveform of the rapid spikes. The pattern of inhibition of the plateau/silent phase cycles by epinephrine is qualitatively different from the pattern seen during inhibition of electrical activity by reducing glucose level. This suggests that the electrical rhythm is controlled by more than one pathway. The persistence of electrical activity at very high levels of epinephrine (to 10,000 nM) suggests that electrical activity and, therefore, Ca2+ uptake can exist in the absence of insulin release.
Diabetes 1982 Nov
PMID:Islet electrical pacemaker response to alpha-adrenergic stimulation. 675 17

Counterregulatory secretion of epinephrine occurs during severe insulin-induced hypoglycemia. Under these conditions (minimal plasma glucose 27.4 +/- 1 mg/dl) the decrease of serum potassium concentration (0.9 mVal/L) is mediated by two mechanisms: insulin-induced (0.48 mVal/L) and epinephrine-induced (0.42 mVal/L) cellular uptake of potassium. Epinephrine-induced serum potassium uptake appears to be more sensitive to beta-adrenoceptor blockade than glucose production. The intensification of insulin-induced hypokalemia by epinephrine is of clinical significance.
Diabetes 1982 Jul
PMID:Regulation of serum potassium during insulin-induced hypoglycemia. 676 Nov 99

To evaluate the effect of epinephrine on the circulating amino acids, we infused epinephrine into normal human subjects and juvenile-onset diabetic patients given a constant basal infusion of insulin. Epinephrine infusion produced an identical 350--400 pg/ml rise in plasma epinephrine in both groups. In normal subjects, epinephrine caused a progressive 26% reduction in total circulating amino acids, despite unchanged levels of plasma insulin. This effect was most pronounced for the branched amino acids, which fell by 40% (P < 0.001). Plasma alanine was the only amino acid which failed to decline. Similarly, infusion of epinephrine in the insulin-infused diabetics produced a 23% fall in total amino acids, a 37% decline in branched chain amino acids, but no change in plasma alanine. Saline infusion in the insulin-infused diabetics had no effect on plasma amino acid concentrations. In addition, when epinephrine was infused into two insulin-withdrawn diabetics, a comparable hypoaminoacidemic response was observed. The infusion of propranolol in both normal and diabetic subjects totally prevented the epinephrine-induced fall in plasma amino acids. It is concluded that (1) increments in epinephrine similar to those observed in stress cause a decline in circulating amino acids (except alanine) which is greatest for the branched chain amino acids; (2) this hypoaminoacidemic effect occurs in the absence of a rise in plasma insulin and diabetic subjects, as well; and (3) epinephrine-induced changes in amino acid regulation are prevented by beta-adrenergic blockade. Our findings suggest that, in contrast with glucose and fat metabolism, epinephrine and insulin may have similar, rather than antagonistic, effects on plasma amino acid metabolism.
Diabetes 1980 Nov
PMID:Epinephrine-induced hypoaminoacidemia in normal and diabetic human subjects: effect of beta blockade. 700 May 85


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>