Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We measured net uptake and release of amino acids in the brain of 7 nondiabetic and six diabetic subjects. Duration of insulin-dependent diabetes (IDDM) was 19.4 +/- 2.1 years. Arteriojugular vein measurements were performed before and after 120 minutes of insulin infusion and ensuing Biostator-regulated normoglycemia. Cerebral blood flow was measured during normoglycemia by 11-CH3-F and positron emission tomography. During hyperglycemia in the IDDM subjects, arterial concentrations of valine and leucine were higher, and those of glutamic acid and arginine lower, than in nondiabetic subjects. Insulin infusion lowered levels of most amino acids in both groups. Insulin treatment did not significantly affect the uptake or release of amino acids. Significant net uptake of branched-chain amino acids was noted in both groups, as well as uptake of lysine and phenylalanine in the IDDM subjects. The sum of measured differences was not different from zero in either group. Nitrogen balance depended on impressive release of glutamine from the brain (-963 +/- 147 and -960 +/- 303 nmol/100 g/min), which amounted to 73% and 69% of net release in nondiabetic and IDDM subjects, respectively. We conclude that balance between uptake and release of amino acids is similar in nondiabetic and in long-term IDDM subjects.
 ...
PMID:Brain uptake and release of amino acids in nondiabetic and insulin-dependent diabetic subjects: important role of glutamine release for nitrogen balance. 153 41

Renal metabolism of amino acids (AAs) was evaluated in 5 patients with early IDDM, and in 7 controls (C) in the basal state for 80 minutes after the ingestion of an AA mixture simulating an animal protein meal. Insulin was withdrawn 20 hours before the study. Renal metabolism of AAs was evaluated by the arterial-venous difference technique. In the basal state in IDDM, as in C, the kidney takes up large amounts of a few nonessential AAs (NEAAs): it releases many NEAAs and a few essential AAs (EAAs). After AA ingestion in C, renal extraction of most EAAs, mainly BCAAs, Lys, and Thr, occurs; Pro extraction also increases and a significant uptake of Gly, Glu, Asp, Orn, and Tyr takes place. EAA extraction accounts for 30-40% of total AA uptake. In IDDM, after AA ingestion, a) renal uptake of total AAs is significantly lower, owing mainly to a markedly lower uptake of BCAAs, Lys, and also of Pro, Orn, and Ala; b) renal EAA uptake accounts for less than 20% of total AA extraction. These results indicate that in IDDM postprandial renal N repletion is impaired and unbalanced.
 ...
PMID:Renal metabolism of amino acids in early insulin-dependent diabetes mellitus. 177 10

Structure elucidation of a specific fluorophore from the aging extracellular matrix revealed the presence of a protein crosslink formed through nonenzymatic glycosylation of lysine and arginine residues. The unexpected finding that a pentose instead of a hexose is involved in the crosslinking process suggested that the crosslink, named pentosidine, might provide insight into abnormalities of pentose metabolism in aging and disease. This hypothesis was investigated by quantitating pentosidine in hydrolysates of 103 human skin specimens obtained randomly at autopsy. Pentosidine level was found to increase exponentially from 5 to 75 pmol/mg collagen over lifespan (r = 0.86, P less than 0.001). A three- to tenfold increase was noted in insulin-dependent diabetic and nondiabetic subjects with severe end-stage renal disease requiring hemodialysis (P less than 0.001). Moderately elevated levels were also noted in some very old subjects, some subjects with non-insulin dependent diabetes, and two subjects with cystic fibrosis and diabetes. The cause of the abnormal pentose metabolism in these conditions is unknown but may relate to hemolysis, impaired pentose excretion, cellular stress, and accelerated breakdown of ribonucleotides. Thus, pentosidine emerges as a useful tool for assessment of previously unrecognized disorders of pentose metabolism in aging and disease. Its presence in red blood cells and plasma proteins suggests that it might be used as a measure of integrated pentosemia in analogy to glycohemoglobin for the assessment of cumulative glycemia.
 ...
PMID:End-stage renal disease and diabetes catalyze the formation of a pentose-derived crosslink from aging human collagen. 229 12

Fasting plasma zinc levels were determined in 45 IDDM and in 40 NIDDM patients. Mean values were similar in both groups, but diabetic men showed a significantly higher plasma zinc (p less than 0.05) than diabetic women. In patients with diabetic nephropathy a lower zinc level was associated with decreased plasma albumin as compared to patients without complications (p less than 0.001). Neuropathy and macro-angiopathy were also associated with lower zincemia (p less than 0.05) but in the presence of normal albumin levels. In IDDM without nephropathy a significant positive correlation was found between plasma zinc and plasma glucose, albumin, branched chain amino acids and glutamine, while in NIDDM without nephropathy a significant positive correlation exists between plasma zinc and the amino acids glutamine, valine, histidine and lysine.
 ...
PMID:Plasma zinc levels in diabetes mellitus: relation to plasma albumin and amino acids. 375 14

This study compares the utility of nonenzymatically glycosylated serum proteins (lys-GSP) to glycosylated hemoglobins (HbA1a-c) as control indices of glucose homeostasis in patients with IDDM. The diagnostic value of lys-GSP was also examined in patients with non-insulin-dependent diabetes mellitus, in subjects with impaired glucose tolerance, and in two patients with insulinoma. The intraindividual fluctuation of lys-GSP in normoglycemic subjects is very small, resulting in an interindividual range of 3.0 +/- 0.3 lysine-bound glucose/mg protein (means +/- SD, N = 52). HbA1a-c with a normal range of 6.4 +/- 0.9% (N = 52) shows greater variability. In IDDM there is no overlap of lys-GSP levels between the normal and the diabetic range at the 95% confidence level. In patients treated with an open-loop insulin delivery system failure of normalization of the glucose balance was clearly discernible by an elevation of GSP. In contrast, in about 40% of the patients with incomplete glycemic control the HbA1a-c levels fell within the normal range. The utility of lys-GSP for diagnosis of diabetes is compared with the results of 60 oral glucose tolerance tests. Two patients suffering from insulinoma displayed decreased lys-GSP values. From these results it appears that determination of lys-GSP represents a more sensitive parameter for long-term control than HbA1a-c and is suitable for monitoring even small fluctuations of blood glucose.
 ...
PMID:Clinical utility of nonenzymatically glycosylated blood proteins as an index of glucose control. 651 Jan 80

The aim of these studies was to compare the pharmacokinetics, pharmacodynamics, counterregulatory hormone and symptom responses, as well as cognitive function during hypoglycaemia induced by s.c. injection of 0.15 IU/kg of regular human insulin (HI) and the monomeric insulin analogue [Lys(B28),Pro (B29)] (MI) in insulin-dependent-diabetic (IDDM) subjects. In these studies glucose was infused whenever needed to prevent decreases in plasma glucose below 3 mmol/l. After MI, plasma insulin increased earlier to a peak (60 vs 90 min) which was greater than after HI (294 +/- 24 vs 255 +/- 24 pmol/l), and plasma glucose decreased earlier to a 3 mmol/l plateau (60 vs 120 min) (p < 0.05). The amount of glucose infused to prevent plasma glucose falling below 3 mmol/l was approximately three times greater after MI than HI (293 +/- 26 vs 90 +/- 25 mumol.kg-1 x 60-375 min-1, p < 0.05). After MI, hepatic glucose production was more suppressed (0.7 +/- 1 vs 5.9 +/- 0.54 mumol.kg-1.min-1) and glucose utilization was less suppressed than after HI (11.6 +/- 0.65 vs 9.1 +/- 0.11 mumol.kg-1.min-1) (p < 0.05). Similarly, plasma NEFA, glycerol, and beta-OH-butyrate were more suppressed after MI than HI (p < 0.05), whereas plasma lactate increased only after MI, but not after HI. Responses of counterregulatory hormones, symptoms and deterioration in cognitive function during plasma glucose plateau of 3 mmol/l were superimposable after MI and HI (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Pharmacokinetics, pharmacodynamics and glucose counterregulation following subcutaneous injection of the monomeric insulin analogue [Lys(B28),Pro(B29)] in IDDM. 795 44

Insulin lispro [Lys (B28), Pro (B29) human insulin] is a rapidly absorbed analog that has diminished tendency to self-associate. In four open-label, 1-year-long international randomized trials, we contrasted the immunogenicity of insulin lispro versus regular human insulin (RHI) in patients previously treated with insulin who had IDDM or NIDDM. Using a self-blank subtraction assay, we assessed sera for the presence of insulin-specific antibodies (ISA), insulin lispro-specific antibodies (LSA), and cross-reactive antibodies (CRA). Basal insulin needs were provided either with human ultralente (UL) or NPH insulins. After 2 to 4 weeks of therapy with RHI plus UL or RHI plus NPH, 50% of patients were randomly assigned to begin insulin lispro or continue on RHI. At baseline, few pretreated patients had LSA (0-4%) and approximately 10% had ISA, whereas 41-45% of patients with IDDM and 23-27% of patients with NIDDM had CRA (IDDM vs. NIDDM, P < 0.001). Within studies, no significant differences were noted over time in ISA, LSA, or CRA attributable to the type of short-acting insulin. When data were pooled, inconsistent changes were noted in ISA and LSA (LSA were greater in NIDDM vs. IDDM at baseline, P = 0.001, and ISA were greater in IDDM vs. NIDDM at 6 months, P = 0.007). Significant levels of CRA were more common in IDDM at all times (P < 0.001, P = 0.022, and P = 0.002 at baseline, 6 months, and 12 months, respectively). For patients receiving insulin lispro, no significant changes occurred in antibody status among IDDM and NIDDM patients throughout the study (became positive, remained positive, became negative, or remained negative). IDDM patients were more likely to develop or maintain CRA levels (P = 0.008 vs. NIDDM), whereas antibody levels were comparable among positive individuals. No evidence was noted that insulin lispro differs in immunogenicity from RHI in previously treated IDDM and NIDDM patients.
 ...
PMID:Immunologic effects of insulin lispro [Lys (B28), Pro (B29) human insulin] in IDDM and NIDDM patients previously treated with insulin. 892 61

Glycated haemoglobin (HbA1c) measured by high performance liquid chromatography (HPLC) in a 20 year old female with insulin dependent diabetes mellitus was consistently within the normal range although her daily blood glucose values were > 11.1 mmol/l. HbA1c measured by immunoagglutination and fructosamine was elevated and correlated with the patient's blood glucose values. The HPLC chromatogram showed an additional peak at HbA0. Electrophoresis of haemoglobin on citrate agar gel revealed an abnormal haemoglobin anodal of HbS. Cellulose acetate electrophoresis and isoelectric focusing demonstrated an additional haemoglobin migrating close to HbA2. Amino acid analysis and DNA sequencing revealed an alpha 30 (B11) Glu-->Lys replacement, that is, haemoglobin O Padova. Investigations of two family members without diabetes revealed the same rare haemoglobin variant. This case showed that this silent haemoglobin mutation caused an additional peak and falsely low HbA1c values when measured by HPLC, the gold standard for this evaluation.
 ...
PMID:Haemoglobin O Padova and falsely low haemoglobin A1c in a patient with type I diabetes. 921 29

Insulin lispro, a recombinant insulin analogue, is identical to human insulin except for the transposition of proline and lysine at positions 28 and 29 in the C-terminus of the B chain. The resultant reduced capacity for self-association in solution translates into more rapid absorption of insulin lispro than human regular insulin from subcutaneous sites. Maximum insulin concentrations are higher and are reached earlier with insulin lispro than with human regular insulin, and insulin concentrations return to baseline values more quickly with insulin lispro; consequently, insulin lispro has a more rapid onset and a shorter duration of glucose-lowering activity. These pharmacological properties provided the rationale for comparative clinical trials of subcutaneous insulin lispro (administered within 15 minutes before meals, preferably immediately before meals) and subcutaneous human regular insulin (administered 20 to 45 minutes before meals) in patients with type 1 diabetes (insulin-dependent diabetes mellitus) or type 2 diabetes (non-insulin-dependent diabetes mellitus) requiring premeal insulin therapy plus basal insulin therapy. Available clinical trials are well designed and results suggest that 1- and 2-hour postprandial blood glucose levels with insulin lispro are similar to or lower than those with human regular insulin; 1- and 2-hourpostprandial glucose excursions are similar to or less pronounced than those with human regular insulin. Glycated haemoglobin A values were generally similar with both agents. Continuous subcutaneous insulin infusion was associated with greater improvements in postprandial blood glucose levels and glycated haemoglobin A1 values with insulin lispro than with human regular insulin. Confirmatory data are required. The incidence of hypoglycaemia with insulin lispro was similar to or lower than that with human regular insulin. In particular insulin lispro appears to be associated with a lower incidence of night-time and severe hypoglycaemic episodes. Evidence also suggests that patients perceive their quality of life to be improved with insulin lispro compared with human regular insulin, and that satisfaction with treatment is greater with the insulin analogue. Thus, in patients with type 1 or 2 diabetes requiring premeal insulin therapy, insulin lispro appears to provide greater postprandial glycaemic control than human regular insulin without increasing the risk of hypoglycaemia. Furthermore, the reduced injection-meal interval with this agent offers greater convenience for the patient than regular human insulin. If longer term clinical experience supports these promising results it is likely that insulin lispro will offer important advantages over human regular insulin.
 ...
PMID:Insulin lispro: a review of its pharmacological properties and therapeutic use in the management of diabetes mellitus. 933 63

[Nepsilon-palmitoyl Lys (B29)] human insulin is a fatty acid-acylated derivative of insulin with extended action compared to unmodified insulin when infused intravenously (i.v.) secondary to its binding to circulating albumin. The duration and activity profile of the acylated (A) and NPH (B) insulins were assessed following subcutaneous (s.c.) doses of (A) 6 nmol/kg and (B) 1.2 nmol/kg (equivalent to 0.2 U/kg) in 9 subjects with IDDM. After overnight i.v. infusion of regular human insulin, morning glucose was (A) 6.9 +/- 0.1 and (B) 6.8 +/- 0.1 mmol/l. After the s.c. injection, i.v. human insulin or glucose was infused to maintain near-basal glycaemia and tracer glucose to assess hepatic glucose production (HGP). An activity profile was deduced for each study by expressing the glucose infusion rate at each time point, as a fraction (%) of the basal (measured) HGP, and the i.v. insulin infusion rate as a fraction (%) of the basal requirement. The two fractions are combined by adding the fractional glucose infusion rate and subtracting the fractional insulin infusion rate. Infusion rates of i.v. insulin in the morning were (A) 0.96 +/- 0.096 and (B) 1.22 +/- 0.09 pmol x kg(-1) x min(-1). After insulin injection, i.v. insulin requirements decreased and were below 10% of basal between 100 and 150 min. A constant activity profile of 0% represents a perfect substitution of the basal i.v. insulin infusion by the s.c. dose. The actual profile is defined by deviations from this (above) and was -17 +/- 11, 7 +/- 10, -9 +/- 6 and -18 +/- 18% for [Nepsilon-palmitoyl Lys (B29)] human insulin and 17 +/- 12, 5 +/- 6, -9 +/- 15, 22 +/- 18% for NPH insulin at 3, 6, 9 and 12 h after s.c. injection. HGP was similar for the two insulins, demonstrating similar metabolic actions and profiles both peripherally and at the liver.
 ...
PMID:Basal activity profiles of NPH and [Nepsilon-palmitoyl Lys (B29)] human insulins in subjects with IDDM. 949 40


1 2 3 4 5 6 7 8 Next >>