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

Mucormycosis (synonymous with phycomycosis and zygomycosis) is a devastating fungal infection which usually involves patients with diabetes mellitus, often complicated by ketoacidosis, and malignant neoplasms, commonly leukemia and lymphoma. Clinical manifestations include rhinocerebral, pulmonary, disseminated, isolated cerebral, gastrointestinal and cutaneous disease. Common to all forms of mucormycosis is vascular invasion with production of necrotic tissue. The diagnosis is achieved by demonstrating broad, non-septate hyphae with right-angle branching in a tissue biopsy specimen. Successful treatment consists of early diagnosis, intensive systemic antifungal therapy with amphotericin B, aggressive surgical debridement and control of the underlying disease. In our experience with mucormycosis at Huntsville Hospital, the patients were immuno- compromised and the infection was restricted to the lung. Despite use of amphotericin B in all patients, the only one who survived underwent surgical section of infected tissue.
Ala Med
PMID:Mucormycosis: a community hospital perspective. 223 27

To assess the mechanisms responsible for increased gluconeogenesis in noninsulin-dependent diabetes mellitus (NIDDM), we infused [3-14C]lactate, [3-13C]alanine, and [6-3H]glucose in 10 postabsorptive NIDDM subjects and in 9 age- and weight-matched nondiabetic volunteers and measured systemic appearance of alanine and lactate, their release from forearm tissues, and their conversion into plasma glucose (corrected for Krebs cycle carbon exchange). Systemic appearance of lactate and alanine were both significantly greater in diabetic subjects (18.2 +/- 0.9 and 5.8 +/- 0.4 mumol/kg/min, respectively) than in the nondiabetic volunteers (12.6 +/- 0.7 and 4.2 +/- 0.3 mumol/kg/min, respectively, P less than 0.001 and P less than 0.01). Conversions of lactate and alanine to glucose were also both significantly greater in NIDDM subjects (8.6 +/- 0.5 and 2.4 +/- 0.1 mumole/kg/min, respectively) than in nondiabetic volunteers (4.2 +/- 0.4 and 1.8 +/- 0.1 mumol/kg/min, respectively, P less than 0.001 and P less than 0.025). The proportion of systemic alanine appearance converted to glucose was not increased in NIDDM subjects (42.7 +/- 1.9 vs. 44.2 +/- 2.9% in nondiabetic volunteers), whereas the proportion of systemic lactate appearance converted to glucose was increased in NIDDM subjects (48.3 +/- 3.8 vs. 34.2 +/- 3.8% in nondiabetic volunteers, P less than 0.025); the latter increased hepatic efficiency accounted for approximately 40% of the increased lactate conversion to glucose. Neither forearm nor total body muscle lactate and alanine release was significantly different in NIDDM and nondiabetic volunteers. Therefore, we conclude that increased substrate delivery to the liver and increased efficiency of intrahepatic substrate conversion to glucose are both important factors for the increased gluconeogenesis of NIDDM and that tissues other than muscle are responsible for the increased delivery of gluconeogenic precursors to the liver.
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PMID:Mechanism of increased gluconeogenesis in noninsulin-dependent diabetes mellitus. Role of alterations in systemic, hepatic, and muscle lactate and alanine metabolism. 225 58

Insulin resistance is an early predictor of development of noninsulin-dependent diabetes mellitus (NIDDM) in Pima Indians, a population with the highest reported prevalence of NIDDM. The insulin receptor plays a central role in mediating insulin action, and previous studies have demonstrated that mutations in the insulin receptor gene may cause insulin resistance. Therefore, we have cloned the insulin receptor cDNA from an insulin-resistant Pima Indian to determine if there is a mutation in the patient's insulin receptor gene. We obtained nine cDNA clones spanning exons 4-10 and 12-22 of the patient's insulin receptor gene. Polymorphisms in the nucleotide sequences for codons 523 (Ala), 1058 (His), and 1062 (Leu) provided useful markers to differentiate the patient's two alleles of the insulin receptor gene. These substitutions were silent, in that they did not alter the predicted amino acid sequence. The sequence of exons 1-3 and 11 was determined directly from genomic DNA that had been amplified using the polymerase chain reaction catalyzed by Taq DNA polymerase. Other investigators have reported defects in insulin binding and insulin receptor tyrosine kinase activity in diabetic Pima Indians. However, we did not detect any mutations in this patient's insulin receptor gene. Thus, these observations are consistent with the interpretation that the defects in insulin receptor function are acquired rather than derived from defects in the primary structure of the receptor.
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PMID:The amino acid sequence of the insulin receptor is normal in an insulin-resistant Pima Indian. 231 37

Variations in the incidence rate of Type 1 (insulin-dependent) diabetes mellitus might relate to ethnic-specific genetic backgrounds. HLA-DQB 1 alleles were typed in 75 French diabetic children and 85 matched control children. Enzymatically-amplified DQB 1 exon 2 was hybridized with oligoprobes specific for the six most common alleles. Alleles coding for an Asp residue at position 57 in the DQ beta chain are strongly negatively associated with Type 1 diabetes in the French population. Nevertheless, one of the diabetic children was an Asp 57 homozygote (DQB 1.2/3.1). Among alleles coding for a residue other than Asp at position 57, alleles 3.2 and 2 (Ala 57) are positively associated with diabetes but not allele 1.1 (Val 57) which is less frequent in diabetic children than in control children. Heterozygosity for 2/3.2 alleles is the genotype most strongly associated with diabetes (Odds ratio = 52.9). Large comparative population studies will be necessary to determine whether the frequency of DQB 1 alleles positively associated with Type 1 diabetes (2 and 3.2) in a given ethnicity is related to its incidence rate in the same population.
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PMID:HLA-DQB 1 codon 57 and genetic susceptibility to type 1 (insulin-dependent) diabetes mellitus in French children. 232 49

Eleven insulin-dependent diabetes mellitus (IDDM) patients with angiographically normal coronary arteries and a normal hemodynamic response to an echocardiographic-dipyridamole test and 12 normal controls were studied at rest and after atrial pacing simultaneously sampling arterial and coronary sinus blood. In IDDM patients, despite hyperglycemia [10.0 +/- 2.0 (SE) mmol/l], myocardial glucose uptake was slightly lower than in controls. This process was significantly activated in both groups during atrial pacing. The isotopically calculated net flux of lactate across myocardium, in agreement with the net balance value based on unlabeled lactate-pyruvate arteriovenous differences, showed a net uptake in controls (3.5 +/- 0.6 mumol.min-1.1.73 m-2) and a net release in IDDM (12.4 +/- 2.6; P less than 0.01). Atrial pacing stimulated lactate uptake in both groups. Myocardial uptake of ketone bodies was significantly higher in IDDM (37.0 +/- 6.3 mumol.min-1.1.73 m-2) than in controls (10.1 +/- 3.4 mumol.min-1.1.73 m-2; P less than 0.01). Free fatty acid uptake was also significantly greater in IDDM than in controls (44.1 +/- 7.0 vs. 24.1 +/- 5.1 mumol.min-1.1.73 m-2; P less than 0.01). Alanine and branched amino acids were released by diabetic but not by control hearts at rest. The normalization of blood glucose concentrations restored normal patterns of lactate and ketone body kinetics across diabetic myocardium. In conclusion, 1) at rest, myocardial lactate and amino acid uptake is markedly impaired in IDDM without coronary artery disease, and 2) the metabolic abnormalities of the diabetic myocardium are not a primary phenomenon but rather a consequence of hypoinsulinemia and hyperglycemia because insulin administration, resulting in euglycemia, restored normal patterns of cardiac metabolism.
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PMID:Myocardial metabolism in insulin-deficient diabetic humans without coronary artery disease. 233 60

Branched-chain alpha-keto acid dehydrogenase (BCKAD) is a multisubunit complex regulated by phosphorylation and is considered to be rate-limiting for branched-chain amino acid (BCAA) metabolism in skeletal muscle. Glucocorticoids increase net protein degradation in muscle; associated with this increased breakdown of muscle protein is an elevated rate of BCAA oxidation. The effects of glucocorticoids on skeletal muscle BCKAD were investigated in different rat models. BCKAD was activated after glucocorticoid treatment (both acutely, within 2 h, and chronically). The amount of enzyme per muscle cell increased after 5 d of cortisone acetate treatment. Insulin administration partially blocked the acute effects of glucocorticoids on muscle BCKAD. Activation was also observed during metabolic acidosis, insulinopenic diabetes mellitus, and endotoxic shock, three conditions characterized by elevated circulating glucocorticoids, increased BCAA oxidation, and increased net protein breakdown. Activation of BCKAD may account for the increased oxidation of BCAA observed during hypercortisolemia. The sequelae of this accelerated catabolism may include increased glutamine and alanine production for gluconeogenesis and provision of ATP for muscle work.
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PMID:Glucocorticoid regulation of muscle branched-chain amino acid metabolism. 238 1

A group of 15 patients with controlled insulin-independent diabetes (Type 2) were workloaded submaximally by a 15-minute load on a cycle ergometer and 2-3 days later same workload was repeated, but this time 5-patient groups were administered before the workload: 0.1 j.m. of insulin/kg of body mass i.v., 1.0 g tolbutamide sodium i.v. and 150 mg of phenformin orally one hour before the load. The patients who were injected insulin or tolbutamide were also administered glucose solution (intravenously) so as to keep the same level of glycaemia as in the follow-up examination. The time of metabolic observation after workload was 90 min., so the whole examination took 105 minutes. In the first (follow-up) examination, all the probands had in the venous blood an increase in alanine, lactate, pyruvate and the relation lactate: pyruvate (L/P), a decrease in pH, bicarbonates and pO2 (in capillary afterialized blood). The administration of insulin and tolbutamide eliminated or reduced after-effort alaninaemia increase, whereas the administration of phenformin increased the concentration of this amino acid in the blood after effort. Insulin resulted in a greater increase in after-effort lactacidaemia; besides, insulin and tolbutamide increased the relation L/P during and after effort. The influence of antidiabetic drugs on the behaviour of other biochemical parameters after effort was insignificant. The results obtained show that antidiabetic drugs modify the increase in alaninaemia after effort in patients with controlled insulin-independent diabetes (Type 2), the direction of the modification depending on a specific influence of particular drugs on the metabolism of this amino acid. While evaluating the influence of effort on the concentration of alanine in the blood in patients with this type of diabetes one should consider not only the present demand for this gluconeogenes substrate but also a specific influence of the kind of therapy applied at the time.
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PMID:[Effect of antidiabetics on post-exercise alaninemia in patients with non-insulin-dependent diabetes mellitus (type 2)]. 251 27

Adult male and female rats were used as test animals. The experimental diabetes mellitus was provoked with one dose of i.v. injection of streptozotocin (65 mg/kg body weight), which interferes with the insulin release mechanism in pancreatic beta cells. After a follow-up period of 10 wk an average loss of 10% of body weight and an increase of 25% in the amount of blood obtained by decapitation was recorded in the test animals. The biochemical assays performed on the serum of the diabetic rats showed, for both sexes, a fourfold rise in the plasma glucose level, a threefold rise in plasma alkaline phosphatase activity and plasma alanine transferase activity as well as a 1.5-fold rise in plasma creatine value. The two latter values indicated systematic disorders reflected in the liver and the kidneys. An increase in serum total calcium and hydroxyproline values was also detected. The clinical studies of the gingiva showed diminished tissue resistance in diabetic rats. The histologic studies of alveolar bone revealed retarded formation of bone matrix and new bone in diabetic animals. However, the stimulated metabolism in alveolar bone, due to the artificially induced stress, increased marginal bone cell activity in both the diabetic and the control group, resulting in increased crestal resorption in the former group. The differences in tissue response observed among the diabetic animals affected and unaffected by stress originated from the disturbed recovering mechanism typically found in diabetic animals.
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PMID:Impact of streptozotocin-induced diabetes on rat blood and alveolar bone affected by occlusal stress. 252 6

Plasma glucose and insulin responses to a muscarinic agonist (bethanechol chloride) and a muscarinic antagonist (atropine) were evaluated in obese C57BL/6J ob/ob mice and in lean C57BL/6J + /? mice. In lean +/? mice, plasma glucose decreased in response to 1 and 2 micrograms/g bethanechol chloride, whereas insulin increased significantly. In ob/ob mice, insulin increased remarkably in response to bethanechol administration (saline, 632 +/- 80 microU/ml; 2 micrograms/g bethanechol chloride, 1794 +/- 97 microU/ml; n = 10), but surprisingly, plasma glucose also rose significantly (saline, 230 +/- 14 mg/dl; 2 micrograms/g bethanechol chloride, 363 +/- 18 mg/dl, n = 10). This exaggerated hyperglycemia in ob/ob mice was not associated with significant changes in plasma glucagon. Furthermore, administration of propranolol hydrochloride did not diminish bethanechol chloride-induced hyperglycemia in ob/ob mice. Administration of atropine (2.5, 5, and 10 mg/kg body wt) induced a significant decrease in plasma insulin without changes in plasma glucose in ob/ob mice, whereas neither plasma insulin nor plasma glucose changed in lean mice. Finally, conversion of [14C]alanine to glucose was increased in ob/ob mice after bethanechol chloride administration, indicating that muscarinic stimulation increases gluconeogenesis in an animal model of type II (non-insulin-dependent) diabetes.
Diabetes 1989 Nov
PMID:Muscarinic stimulation and antagonism and glucoregulation in nondiabetic and obese hyperglycemic mice. 257 6

13C-n.m.r. spectroscopy was used to determine the metabolic fate of alanine and aspartate in rat and rabbit kidney proximal tubules. The main purpose of the present study was to investigate the effect of streptozotocin-induced diabetes on the influx of 13C label from [3-13C]alanine into the tricarboxylic acid cycle and through the fructose-1,6-bisphosphatase pathway. This influx was calculated from the relative enrichment of 13C in the various glutamate and glutamine carbon atoms. The relative proportion of 13C label which entered the tricarboxylic acid cycle via pyruvate carboxylase relative to the proportion that entered via pyruvate dehydrogenase was 1.92 +/- 0.02 in fed control rats and 2.27 +/- 0.04 in streptozotocin-treated rats. However, streptozotocin-induced diabetes did not significantly affect this ratio in rabbit proximal convoluted tubular cells. Only in rat proximal convoluted tubular cells did we observe an increase in flux through the fructose-1,6-bisphosphatase pathway by streptozotocin treatment compared with fed controls. The data suggest that streptozotocin-induced diabetes in rats causes the same metabolic changes as does chronic acidosis.
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PMID:A 13C-n.m.r. investigation of the metabolism of amino acids in renal proximal convoluted tubules of normal and streptozotocin-treated rats and rabbits. 260 95


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