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

To evaluate effects of acute loading of different proteins on renal function, glomerular filtration rate (GFR), albumin excretion rate (AER), and concentrations of plasma amino acids, 11 normal volunteers and 20 diabetic patients were studied before and after eating 1.0 g/kg body weight of either tuna fish meal or bean curd on separate days. In normal subjects, the mean baseline GFR was 115.8 +/- 9.5 ml/min/1.73 m2, and the mean GFRs after ingestion of tuna fish meal were 134.1 +/- 15.5 (1 hr), 146.2 +/- 18.8 (2 hr), and 157.8 +/- 21.2 (3 hr), respectively. GFR did not significantly increase in normal subjects after ingestion of bean curd. GFR in diabetic patients with normoalbuminuria after ingestion of each protein was similar to the response in normal subjects. In diabetic patients with microalbuminuria, GFR did not significantly increase after ingestion of each protein. In diabetes with macroalbuminuria, GFR decreased after ingestion of tuna fish meal and did not significantly change after intake of bean curd. In both normal subjects and diabetic patients, urinary AER did not increase after each kind of protein loading. Plasma concentrations of alanine, glycine, and arginine, known to induce glomerular hyperfiltration, increased to a greater degree after ingestion of tuna fish meal than after administration of bean curd. These findings suggest that responses of GFR to acute protein loading may differ according to the amino acid composition of the protein ingested and to the stage of diabetic nephropathy.
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PMID:Effects of acute protein loads of different sources on renal function of patients with diabetic nephropathy. 260 33

DQw8 (DQw3.2) on DR4 haplotypes is a susceptibility gene for development of insulin-dependent diabetes mellitus (IDDM) in Caucasoids, possibly because it encodes a non-Asp amino acid (aa) (i.e. Ala) at residue 57 of the DQ beta chain (non-Asp-57). Most Caucasoid IDDM patients are homozygous non-Asp-57. We have examined 14 Japanese IDDM patients, selected to be either DR4 or DRw9 (associated to IDDM among Japanese). Their DQB1 alleles and the aa encoded by their DQB1 codons 57 were identified, using 11 different sequence-specific oligonucleotide probes. Secondly, they were examined with DQw8 specific T lymphocyte clones and with anti-DQ monoclonal antibodies. The DQB1 genes on their DR4 and DRw9 haplotypes in all cases encoded Asp-57. Two patients were Asp-57 homozygous, the rest were Asp-57/non-Asp-57 heterozygous. The DR4 haplotypes all carried DQw4 (rather than DQw8), and the DRw9 haplotypes all carried DQw9. Furthermore, five of six DRw8 positive patients carried a previously undetected DRw8DQw8 haplotype, where both the DQA1 and DQB1 genes were similar to those usually found on the DR4DQw8 haplotype. Thus, the DR/DQ allele combinations and aa residue 57 of the DQ beta chain of Caucasoid and Japanese IDDM patients are largely different.
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PMID:HLA-DQ antigens and DQ beta amino acid 57 of Japanese patients with insulin-dependent diabetes mellitus: detection of a DRw8DQw8 haplotype. 261 13

GH has been implicated in the pathophysiology of various acute and chronic complications of diabetes mellitus. As a consequence, there has been a great deal of interest in developing methods for suppressing GH secretion in diabetes. SMS 201-995 is a long-acting somatostatin analog which inhibits the secretion of numerous hormones, including GH. To determine the metabolic and hormonal responses to SMS 201-995 independent of endogenous insulin suppression, we studied six patients with insulin-dependent diabetes mellitus while they received 150 micrograms SMS 201-995, sc, daily for an 8-week period. This treatment resulted in no change in 24-h glucose profiles, although the mean insulin dose decreased by 19%, while hemoglobin A1c decreased significantly (0.084 +/- 0.023 to 0.067 +/- 0.011, P = 0.04). The 24-h profiles of blood lactate, plasma free insulin, glucagon, FFA, blood glycerol, and beta-hydroxybutyrate were unchanged, whereas that of blood alanine increased significantly (7.8 +/- 0.4 to 10.6 +/- 0.9 mmol/L.h; P = 0.01). GH secretion declined in five of the six patients; the mean values before and during SMS 201-995 treatment were 102 +/- 23 and 68 +/- 12 micrograms/L.h, respectively (P = NS), for the six patients. [In the five patients in whom GH secretion declined, the mean values before and during SMS 201-995 treatment were 115 +/- 23 and 63 +/- 14 micrograms/L.h, respectively (P = 0.01).] These results suggest that SMS 201-995 may be administered to patients with insulin-dependent diabetes mellitus without a deleterious effect on metabolic control.
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PMID:The effects of SMS 201-995 (sandostatin) on metabolic profiles in insulin-dependent diabetes mellitus. 264 88

The diurnal patterns of relevant metabolites and hormones in five pancreas-kidney-transplanted patients (aged 36 +/- 2 yr, mean +/- SD) with insulin-dependent diabetes mellitus (IDDM) were compared with those in five kidney-transplanted nondiabetic patients (aged 28 +/- 2 yr). The groups were matched for body mass and current dose and type of immunosuppressive treatment. The serum creatinine levels did not differ between the two study groups, but the serum urea level in the nondiabetic patients was slightly but significantly higher than in the diabetic patients. In the pancreas-kidney-transplanted group the investigation was performed 8-47 mo posttransplantation; in the kidney-transplanted nondiabetic patients, 12-18 mo posttransplantation. The mean 24-h levels and rhythms of blood glucose, free fatty acid, 3-hydroxybutyrate, and alanine did not differ between the groups. The mean 24-h levels of blood lactate and glycerol were moderately but significantly higher in the pancreas-kidney-transplanted diabetic patients. At fasting, the level of serum immunoreactive insulin was more than twice as high in the pancreas-kidney-transplanted patients, whereas the plasma C-peptide levels did not differ significantly between the two groups. The meal-induced increases in serum insulin as well as in the plasma C-peptide levels were more marked in the pancreas-kidney-transplanted patients. The findings suggest that the hyperinsulinemia in these patients was due to both the systemic delivery of insulin and an increase in insulin resistance, the latter being particularly apparent in the postprandial phase.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1989 Jan
PMID:Effects of pancreas transplantation on metabolic and hormonal profiles in IDDM patients. 264 63

The degradation of intracellular protein and other cytoplasmic macromolecules in liver is an ongoing process that regulates cytoplasmic mass and provides amino acids for energy and other metabolic uses early in starvation. Cellular proteins are conveniently divided into two general classes according to readily discernable differences in average rates of turnover. A short-lived class, having a half-life of approximately 10 min, comprises about 0.6% of total protein. Its degradation is not physiologically controlled, and the mechanism is probably nonlysosomal in nature. The second or long-lived group, with an average half-life 250 times greater, constitutes more than 99% of the cell's protein. By contrast, its breakdown is strongly regulated, and the site of catabolism is believed to be the vacuolar-lysosomal system. Cytoplasmic sequestration by lysosomes can be divided into two categories; macro- and microautophagy. The first is induced by amino acid and/or insulin deprivation. Amino acids are considered to be primary regulators, since they can control this process over the full range of induced proteolysis in the absence of hormones. Glucagon, cyclic AMP, and beta-agonists also stimulate macroautophagy in hepatocytes but have opposite effects in myocytes. Micrautophagy differs from the former in that the cytoplasmic "bite" is smaller and the uptake process is not acutely regulated. However, the latter does decrease during starvation in parallel with basal proteolysis, effects that might be linked to the loss of endoplasmic reticulum. The primary control of macroautophagy is accomplished through a small group of direct regulators (Leu, Tyr/Phe, Gln, Pro, Met, His, and Trp) and a specific coregulatory action of alanine. As a group, regulatory amino acids produce direct inhibitory responses in the perfused rat liver that are identical to those of the complete amino acid mixture at 0.5x and 4x (times) normal plasma concentrations. However, they lose effectiveness almost completely within a narrow zone centered at normal levels, a loss that can be abolished by the addition of alanine at its normal plasma concentration (0.5 mM). At this level, alanine does not inhibit directly. Interestingly, this zonal loss is also eliminated by insulin. Glucagon, though, specifically blocks the initial inhibition evoked by 0.5x amino acid mixtures and thus induces maximal rates of protein degradation at normal amino acid concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)
Diabetes Metab Rev 1989 Feb
PMID:Mechanism and regulation of protein degradation in liver. 264 36

Excessive hepatic glucose output is an important factor in the fasting hyperglycemia of non-insulin-dependent diabetes mellitus (NIDDM). To determine the relative contributions of gluconeogenesis and glycogenolysis in a quantitative manner, we applied a new isotopic approach, using infusions of [6-3H]glucose and [2-14C]acetate to trace overall hepatic glucose output and phosphoenolpyruvate gluconeogenesis in 14 postabsorptive NIDDM subjects and in 9 nondiabetic volunteers of similar age and weight. Overall hepatic glucose output was increased nearly twofold in the NIDDM subjects (22.7 +/- 1.0 vs. 12.0 +/- 0.6 mumol.kg-1.min-1 in the nondiabetic volunteers, P less than .001); phosphoenolpyruvate gluconeogenesis was increased more than threefold in the NIDDM subjects (12.7 +/- 1.4 vs. 3.6 +/- 0.4 mumol.kg-1.min-1 in the nondiabetic subjects, P less than .001) and was accompanied by increased plasma lactate, alanine, and glucagon concentrations (all P less than .05). The increased phosphoenolpyruvate gluconeogenesis accounted for 89 +/- 6% of the increase in overall hepatic glucose output in the NIDDM subjects and was significantly correlated with the fasting plasma glucose concentrations (r = .67, P less than .01). Glycogenolysis, calculated as the difference between overall hepatic glucose output and phosphoenolpyruvate gluconeogenesis, was not significantly different in the NIDDM subjects (9.9 +/- 0.06 mumol.kg-1.min-1) and the nondiabetic volunteers (8.4 +/- 0.3 mumol.kg-1.min-1). We conclude that increased gluconeogenesis is the predominant mechanism responsible for increased hepatic glucose output in NIDDM.
Diabetes 1989 May
PMID:Predominant role of gluconeogenesis in increased hepatic glucose production in NIDDM. 265 26

Human insulin and its precursor, mini-proinsulin, made with a new biosynthetic method, were tested for their receptor binding, biologic action, and antibody binding ability. The structure of mini-proinsulin is similar to that of proinsulin with a shortened C-peptide, B(1-29)-Ala-Ala-Lys-A(1-21) insulin. The ability of biosynthetic human insulin to bind to receptors, to stimulate 2-deoxyglucose uptake in isolated adipocytes, and to bind to insulin antibody was comparable to that of semisynthetic human insulin. The ability of mini-proinsulin to bind to insulin receptors and to stimulate 2-deoxyglucose uptake in adipocytes was 0.5 and 0.2% that of human insulin, whereas the corresponding abilities of proinsulin were 5 and 3%, respectively. Despite having less receptor binding and biologic activity, mini-proinsulin demonstrated higher affinity for the insulin antibody than did proinsulin. These results suggest that biosynthetic human insulin behaves similarly to semisynthetic human insulin in its receptor binding and biologic activity, and that the shortened C-peptide region reduces receptor binding by fixing or covering the N-terminal region of the A chain, which is important for receptor binding.
Diabetes Res Clin Pract 1989 Jun 20
PMID:Receptor binding and biologic activity of biosynthetic human insulin and mini-proinsulin produced by recombinant gene technology. 266 66

To assess the effects of insulin in stable coronary artery disease (CAD), 2 U i.v. insulin was given to 9 control and 10 CAD patients during coronary sinus catheterization. Hemodynamic and metabolic data were obtained before and for 90 min after insulin injection. Insulin induced no changes in heart rate, mean aortic pressure, rate-pressure product, coronary sinus flow, or coronary resistance. Metabolic changes were similar in both groups and included 1) 30% decrease of arterial glucose (P less than .001) and 3-fold increase of myocardial glucose uptake (P less than .001), 2) 1.5- to 2.5-fold elevation of arterial lactate (P less than .001) and myocardial lactate usage (P less than .001), respectively, 3) 50-70% suppression of arterial levels (P less than .001) and myocardial uptake of free fatty acids (P less than .01), and 4) 10% reduction of myocardial net oxygen consumption (P less than .05). Myocardial citrate efflux increased in the CAD patients (P less than .05), whereas alanine release rose only in control patients (P less than .01), suggesting that glucose enters glycogen production in the CAD patients and pyruvate production in the control patients to a high degree. Myocardial glutamate uptake remained unchanged. In conclusion, insulin sensitivity was not altered in CAD. The insulin-induced shift from myocardial free fatty acid to carbohydrate usage may be beneficial to the ischemic heart by increasing glycogen stores, saving oxygen, and inhibiting an excess free-fatty acid concentration, which may be toxic during ischemia.
Diabetes 1989 Sep
PMID:Cardiac metabolic and hemodynamic effects of insulin in patients with coronary artery disease. 267 Jun 46

The present study investigated whether or not, in addition to the oral glucose tolerance test, oral alanine loading was a useful diagnostic tool for hormonal and metabolic diseases. Fifty g of L-alanine was administered orally in 14 normal, 12 diabetic, and 8 liver cirrhotic subjects. The influence of oral alanine loading on hormones and metabolites was compared with the results of 100 g oral glucose loading. The results obtained were as follows: 1) In the normal subjects and cirrhotics, lactate and pyruvate concentrations gradually increased with time and reached their peak levels at 60 min, whereas they remained unchanged throughout the course in the diabetic group at glucose loading. 2) Alanine administration accelerated ureogenesis but did not affect blood glucose levels. 3) In both glucose and L-alanine administration, free fatty acid, glycerol and ketone body levels declined nonspecifically in all groups. 4) Serum glucagon levels during L-alanine loading increased in all groups, especially in liver cirrhotics. 5) L-alanine was a potent stimulus for insulin secretion in diabetics, while no insulin release during glucose loading was observed. 6) The molar ratio of insulin levels (during glucose loading)/glucagon levels (during L-alanine loading) was a good indicator of systemic glucose homeostasis from the hormonal aspect. It is suggested that, in addition to the oral glucose tolerance test, the oral administration of L-alanine can be a useful tool for the diagnosis of the status in diabetes mellitus and cirrhosis.
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PMID:Pancreatic alpha- and beta-cell function and metabolic changes during oral L-alanine and glucose administration: comparative studies between normal, diabetic and cirrhotic subjects. 267 46

To characterize the effects of artificial beta-cell directed insulin therapy on carbohydrate, lipid and amino acid metabolism, five insulin-dependent diabetic patients were challenged with a 100-g glucose meal while on conventional (single or split mixed insulin injections) therapy and again after 72 hr on an artificial beta-cell unit. It was verified that the high levels of blood glucose of the conventionally treated diabetics were marked reduced toward normal by the artificial beta-cell therapy, while the blood lactate and pyruvate concentrations increased significantly to levels higher than in normal controls. The elevated levels of FFA, glycerol, and ketones in the diabetics under conventional therapy were entirely normalized during the artificial beta-cell regulation. Furthermore, the artificial beta-cell insulin therapy showed capable to restore the abnormalities in the blood profiles of alanine, glutamine and branched-chain amino acids, exceeding in some points the normal response. It was also detected hyperinsulinemia in the diabetics treated with the artificial beta-cell unit and no change in the pancreatic beta-cell function during this period of regulation, evidenced by low and unchanged blood levels of C-peptide. Marked suppression of pancreatic alpha-cell secretion was detected by the significant decrease of the hyperglucagonemia in the conventionally treated diabetics by the artificial beta-cell therapy. These studies reveal that the artificial beta-cell insulin therapy is capable of restoring to normal not only the abnormal glucose metabolism of conventionally treated diabetics, but also other substrate metabolism related to the lipid and protein homeostasis of the organism.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Res 1989 May
PMID:Carbohydrate, lipid and amino acid metabolism of insulin-dependent diabetic patients regulated by an artificial beta-cell unit. 269 78


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