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)

The effects of manganese on [3H]phenylalanine incorporation into protein were studied in pancreatic acini prepared from normal and streptozotocin-induced diabetic rats. In the absence of added Ca2+ manganese exerted a biphasic effect on [3H]phenylalanine incorporation in both groups of acini. Significant stimulation occurred at 3 X 10(-5) M manganese. At higher concentrations manganese inhibited incorporation. The magnitude of stimulation was similar in all acini, whereas the magnitude of inhibition was greater in acini from normal rats. Addition of Ca2+ to incubation media abolished the stimulatory effect of manganese in normal rat acini and greatly enhanced it in diabetic rat acini, significant stimulation now occurring at 10(-5) M manganese. The magnitude of inhibition was again greater in acini from normal rats. Insulin in vivo partially reversed the diabetes-induced alterations in acinar cell responsiveness to manganese. The present findings suggest that streptozotocin-induced diabetes is associated with postreceptor alterations in the pancreatic acinar cells.
 ...
PMID:Manganese action on pancreatic protein synthesis in normal and diabetic rats. 663 86

A series of synthetic peptides corresponding to the amino-terminal sequence of human growth hormone (hGH) has been studied for insulin-potentiating effects using three different bioassay systems: (1) intravenous insulin tolerance tests, (2) insulin binding to specific receptors of hepatic plasma membranes and isolated hepatocytes, and (3) modulation of insulin-dependent glycogen synthase and glycogen phosphorylase in muscle and adipose tissue. The results establish that the minimum active sequence is the hexapeptide (hGH 8-13) containing H2N-Arg-Leu-Phe-Asp-Asn-Ala-COOH and strongly indicate that the insulin-potentiating action of the active peptides is to increase the binding of insulin to specific receptors and thus modulate the action of glycogen synthase and phosphorylase, producing hypoglycemia as the result of increased glycogen storage in liver, muscle, and adipose tissue.
Diabetes 1980 Oct
PMID:The minimal amino acid sequence of the insulin-potentiating fragments of human growth hormone: its mechanism of action. 677 19

The level of nonenzymatically epsilon-lysine-bound glucose (NEBG) of tissue proteins obtained at autopsy has been determined with a specific method recently described. The mean values expressed as nmol lysine-bound glucose per mumol phenylalanine were 34 for tendon, 13 for aorta, 16 for coronary artery, 23.5 for femoral nerve, 10 for glomerular basement membrane, and 30 for lung parenchyma for tissues from nondiabetics and 86, 39.5, 34, 60, 29, and 57 for tissues form diabetics, respectively. NEBG was below detection limit in skeletal muscle from either nondiabetic or diabetic subjects. Tendon and aorta NEBG levels correlated well with those from other tissues (r = 0.8-0.94, except r = 0.68 for glomerular basement membrane). A fairly good correlation was also found when NEBG of aorta was compared with the mean blood sugar level determined during the last weeks of hospitalization. Finally, an arbitrary index of diabetic late complication was compared with NEBG of aorta. There appears to be a tendency of an increase of the index of complications along with an increase in tissue glucosylation. The possible role of nonenzymatic glucosylation in the long-term complication of diabetes is discussed.
Diabetes 1982 Dec
PMID:epsilon-Amino-lysine-bound glucose in human tissues obtained at autopsy. Increase in diabetes mellitus. 681 47

The oxidation of 14C-labelled glucose, beta-hydroxybutyrate and palmitate to CO2 and the incorporation of 14C-labelled amino acid into alkali-soluble protein were studied in aorta from fed and fasted male Sprague-Dawley rats, weighting about 200 g. Substrate oxidation and amino acid incorporation were measured during incubation of rat aorta in vitro for 2-3 h. After fasting for 6 h there was a slight but significant increase in the plasma concentration of beta-hydroxybutyrate. Blood glucose was lowered after 12 h while an increase in the plasma concentration of free fatty acids was found after 24 h. A decrease in the oxidation of glucose in rat aorta was found after fasting for 12 h and with prolonged fasting a further decrease in the aortic glucose oxidation was found. After fasting for 4 days the oxidation of beta-hydroxybutyrate and the incorporation of 14C-leucine and 14C-phenylalanine into protein were reduced in rat aorta while the oxidation of palmitate was not altered. The effects of fasting on substrate oxidation and amino acid incorporation in rat aorta, found in this study are similar to the known effects of diabetes on vascular metabolism.
 ...
PMID:Effect of fasting on the metabolism in rat aorta. 681 91

Rates of proteolysis by hearts obtained from alloxan diabetic rats and perfused as working preparations with buffer simulating control sera were accelerated 30% above identically perfused control hearts. The total homogenate activities of cathepsin D and beta-N-acetylglucosaminidase, assayed in the presence of Triton X-100, decreased 15-35% in diabetic heart, but the activities of these lysosomal enzymes assayable in the absence of detergent were unchanged in the diabetic tissue. The effects of diabetes were examined further by centrifugation of particulate fractions from subtilisin-treated hearts of control and diabetic rats on polyvinylpyrrolidone-coated colloidal silica (Percoll) gradients. Two species of lysosomes were resolved on the basis of their densities. Both dense and buoyant lysosomes accumulated radioactivity when hearts were exposed to [14C]phenylalanine methyl ester. Dense lysosomes (1.06-1.09 g/ml) sedimented with mitochondria while buoyant lysosomes banded with Golgi and sarcolemmal particles (1.02-1.03 g/ml). When particulate fractions of hearts from diabetic animals were layered on the Percoll gradients, total activities of beta-N-acetylglucosaminidase and cathepsin D were decreased from control in buoyant lysosomes, but unchanged in dense lysosomes. These results demonstrated that the increase in proteolysis in the diabetic heart was associated with decreased total activity and latency of cathepsin D and beta-N-acetylglucosaminidase and an increased proportion of dense lysosomes in the particulate fraction.
 ...
PMID:Effects of diabetes on cardiac lysosomes and protein degradation. 686 24

Insulin was tritiated by semisynthetic replacement of the amino-terminal phenylalanine of the B chain with tritiated phenylalanine. At 15 degrees C, (3H) insulin bound to high affinity receptors on IM-9 cultured human lymphocytes with an affinity constant of about 3 x 10(9) M-1, The Scatchard plot was curvilinear. At 37 degrees C, maximal binding occurred after about 15 min of incubation. Binding fell thereafter due to degradation of insulin by the extracellular fluid. The major degradation product after 120 min coeluted with insulin from Sephadex G50 and was precipitated by anti-insulin antibody but to a lesser degree than intact insulin. It had little or no biologic activity as assessed by binding to IM-9 lymphocytes. The cell-associated radioactivity was also eluted as a single peak on Sephadex G-50. In contrast to the degradation product, this material retained its ability to bind to insulin receptors. We deduce that this cell-associated material contains the entire A chain, most of the B chain, and is probably native insulin. These data show that insulin bound to IM-9 lymphocytes remains biologically intact.
Diabetes 1980 Sep
PMID:Binding and degradation of semisynthetic tritiated insulin by IM-9 cultured human lymphocytes. 700 87

Insulin analogues with different amino acids, including threonine, alanine, L-leucine, D-leucine, L-leucine amide, phenylalanine, tri-alanine, or desalanine, at the B-30 position were semisynthesized from pork insulin by the new enzymatic method. The order of ability of the insulin analogues to bind to anti-insulin sera was [AlaB-30] greater than desalanine greater than [ThrB-30] greater than [Ala-Ala-AlaB-30] greater than [D-LeuB-30], [Leu-NH2B-30],[PheB-30] greater than desoctapeptide greater than or equal to [LeuB-30]. The ability of insulin analogues with different amino acids at B-30 to bind to receptors, as well as their biologic potency tested with glucose uptake in isolated rat adipocytes, was comparable among the analogues. These results suggest that [LeuB-30]-insulin demonstrated the least immunoreactivity and has full activity in receptor binding and biologic effect, and that it may be useful for treatment of anti-insulin antibody-mediated insulin resistance.
Diabetes 1981 Jun
PMID:Immunoreactivity and biologic activity of semisynthetic [LeuB-30]-insulin: potential value in the treatment of insulin antibody-mediated insulin resistance. 701 15

Alterations in circulating alkaline phosphatase have been described in both man and the experimental animal with chronic insulin deficiency. We evaluated plasma and tissue alkaline phosphatase levels in freely-fed control, streptozotocin-induced diabetic and insulin-treated diabetic rats, seven weeks after the induction of diabetes. Circulating alkaline phosphatase activity was markedly elevated in the insulin deficient animal (p less than 0.001) and completely normalized following insulin administration. The elevated plasma alkaline phosphatase activity observed in the insulin deficient animals was heat-resistant and phenylalanine-sensitive, a pattern typical of the intestinal isoenzyme. Small intestinal alkaline phosphatase activity was significantly higher (p less than 0.01) in the diabetic animals, but comparable in the insulin-replaced and control rats. The intestinal isoenzyme activity was found to be strikingly insulin-sensitive; withholding insulin therapy for 36 hr prior to sacrifice resulted in an abrupt rise in both plasma and intestinal alkaline phosphatase values comparable to those observed in the insulin-deficient state. In contrast to these observations, skeletal alkaline phosphatase activity was decreased in the insulin deficient animal (p less than 0.01) and this abnormality was corrected by insulin replacement. Neither insulin deficiency nor insulin replacement resulted in any significant changes in the hepatic alkaline phosphatase isoenzyme.
 ...
PMID:Alkaline phosphatase activity in chronic streptozotocin-induced insulin deficiency in the rat: effect of insulin replacement. 703 17

1. Methods are described for monitoring the metabolic flux through phenylalanine hydroxylase, the tyrosine catabolic pathway and phenylalanine: pyruvate transaminase in isolated liver cell incubations. 2. The relationship between hydroxylase flux and phenylalanine concentration is sigmoidal. 3. Glucagon increases hydroxylase activity at low, near-physiological, substrate concentrations only. The hormone does not affect the rate of formation of phenylpyruvate. 4. Experimental diabetes (for 10 days) increases phenylalanine catabolism, and this is further increased by glucagon. 5. These results are discussed in the light of the known mechanisms for control of phenylalanine hydroxylase activity in vitro.
 ...
PMID:Phenylalanine metabolism in isolated rat liver cells. Effects of glucagon and diabetes. 732 31

To assess how noninsulin-dependent diabetes mellitus (NIDDM) and diabetes control may alter whole body and skeletal muscle proteolysis, we measured the rate of appearance (Ra) of phenylalanine (reflecting proteolysis) in the whole body and across the leg (reflecting skeletal muscle), using a constant tracer infusion of [2H5]phenylalanine in the basal state and during high-dose euglycemic hyperinsulinemia in 6 NIDDM and 10 control subjects. Studies were performed in NIDDM subjects 2 weeks after complete withdrawal of antidiabetic treatment and again after intensive insulin therapy. After intensive treatment, significant reductions were measured in hemoglobin A1C, fasting glucose concentrations, and basal hepatic glucose output. In contrast, there was no change after therapy in basal whole body or leg phenylalanine Ra. Compared with that of controls, whole body phenylalanine Ra was significantly higher and leg phenylalanine Ra significantly lower in NIDDM subjects. During euglycemic hyperinsulinemia, whole body phenylalanine Ra was significantly suppressed (approximately 15%) below basal values before and after therapy in NIDDM subjects and similarly suppressed in control subjects. However, in NIDDM subjects, euglycemic hyperinsulinemia did not reduce leg phenylalanine Ra below basal values either before or after therapy, whereas hyperinsulinemia resulted in a 42% suppression of leg phenylalanine Ra in controls. We conclude that 1) the clear improvement in glucose metabolism produced by intensive insulin therapy in NIDDM is not accompanied by changes in whole body or skeletal muscle proteolysis; 2) skeletal muscle proteolysis is reduced even though whole body proteolysis is increased in NIDDM subjects compared with controls; and 3) although a high-dose systemic infusion of insulin significantly reduces whole body proteolysis in both NIDDM and control subjects, skeletal muscle proteolysis is suppressed only in controls. We speculate that in NIDDM, high basal insulin concentrations (approximately 200 pmol/L, unaltered by therapy) maximally suppress skeletal muscle proteolysis, and therefore higher insulin concentrations produce no additional suppression in skeletal muscle.
 ...
PMID:Skeletal muscle proteolysis is reduced in noninsulin-dependent diabetes mellitus and is unaltered by euglycemic hyperinsulinemia or intensive insulin therapy. 762 32


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