The Metabolism of Amino Acids in Diabetes Mellitus

Luetscher, Jr. John A.

doi:10.1172/jci101300

Cited by 46 publications

(19 citation statements)

References 12 publications

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“…These studies have highlighted the impact of amino acids on the actions of insulin and consequently glucose metabolism. In the 1940s, Luetscher (1942) already reported higher amino acid levels among diabetic patients, and this finding was later confirmed by the demonstration of the positive correlation between amino acid levels and insulin (Felig et al 1969). Furthermore, the i.v.…”

Section: Patient Investigationsmentioning

confidence: 76%

Metabolomics in diabetes research

Friedrich¹

2012

Journal of Endocrinology

124

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Diabetes represents one of the most important global health problems because it is associated with a large economic burden on the health systems of many countries. Whereas the diagnosis and treatment of manifest diabetes have been well investigated, the identification of novel pathways or early biomarkers indicative of metabolic alterations or insulin resistance related to the development of diabetes is still in progress. Over half of the type 2 diabetes patients show manifestations of diabetes-related diseases, which highlight the need for early screening markers of diabetes. During the last decade, the rapidly growing research field of metabolomics has introduced new insights into the pathology of diabetes as well as methods to predict disease onset and has revealed new biomarkers. Recent epidemiological studies first used metabolism to predict incident diabetes and revealed branched-chain and aromatic amino acids including isoleucine, leucine, valine, tyrosine and phenylalanine as highly significant predictors of future diabetes. This review summarises the current findings of metabolic research regarding diabetes in animal models and human investigations.

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Section: Patient Investigationsmentioning

confidence: 76%

Metabolomics in diabetes research

Friedrich¹

2012

Journal of Endocrinology

124

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“…Amino acid concentrations in the urine of nonketotic diabetic patients, however, have not seemed abnormal [6][7][8]. Hyperaminoaciduria, when observed in diabetic patients, usually is associated with ketosis, and is characterized by a nonspecific loss of many amino acids [8,9]. The effect of diabetes on excretion of free amino acids by animals has not been studied previously.…”

Section: Discussionmentioning

confidence: 99%

“…Aminoaciduria, when observed in diabetics, usually has been associated with ketosis [8,9]. The effect of diabetes on the excretion of free amino acids by animals has not been described previously.…”

Section: Introductionmentioning

confidence: 99%

Abnormal amino acid concentrations in plasma and urine of experimentally diabetic dogs

Kern

Engerman

1983

Res. Exp. Med.

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Free amino acid concentrations have been determined in plasma and urine of nonketotic, severely diabetic dogs and age-matched normal controls. Plasma from fasted (as well as fed) diabetics contained supranormal concentrations of several amino acids, including the branched-chain amino acids. In contrast to other species, however, the concentration of only one plasma amino acid (tryptophan) was subnormal in fasted diabetic dogs. Urine collected at the same time showed that the excretion of most amino acids was not abnormal in diabetes. Urinary concentrations of some amino acids were not abnormal despite supranormal levels in plasma. Nevertheless, eight of the 21 amino acids studied reached concentrations significantly greater than normal in the urine of diabetic dogs. Six of the eight amino acids (arginine, histidine, phenylalanine, tyrosine, tryptophan, glutamic acid) showed elevated concentrations in urine even though their plasma concentrations were not elevated. The observed disturbance in the urine/plasma ratio of certain amino acids suggests a possible defect in the renal handling of amino acids in diabetes.

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“…respectively. Since elevated plasma amino nitrogen concentrations in patients with diabetic ketoacidosis have been reported, 16 it is conceivable that the elevated initial GH levels in the present series were due to endogenous elevation of the plasma amino acid levels.…”

Section: Discussionmentioning

confidence: 67%

Diabetic Ketosis: Serial Plasma Growth Hormone Concentrations During Therapy

Cryer

Daughaday

1970

Diabetes

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Plasma growth hormone (GH) concentrations were measured serially during therapy in twelve cases of diabetic ketosis. The initial plasma GH levels varied widely, ranging from 2 to 215 ng,/ml., and were not related to the clinical severity of the ketosis, the degree of depression of the serum bicarbonate, or the magnitude or the hyperglycemia. An increase in the plasma GH concentration followed the institution of insulin therapy in ten of twelve cases. This rise was associated with a fall in the plasma glucose concentration though the latter reached hypoglycemic levels in only one instance. There was no relationship between the total insulin administered during the first twelve hours of therapy and the area under the GH curve for the same period or the initial or peak plasma GH concentration. Thus, despite its known diabetogenic effect and the frequent occurrence of elevated plasma concentrations in ketotic diabetics, growth hormone cannot be a constant major determinant of the insulin resistance of diabetic ketosis. DIABETES 19:519-23, July, 1970.The antagonistic effect of growth hormone (GH) on glucose utilization has been well established in studies of acromegalic, normal, and hypopituitary patients. 1 * 2 Indeed, impaired glucose tolerance has been demonstrated less than two hours after the intravenous injection of 5 mg. of human growth hormone into normal subjects. 3 It is conceivable, therefore, that an acute increase in endogenous growth hormone secretion could contribute to the insulin resistance which typifies moderate to severe diabetic ketosis. The observation that the plasma GH concentration increases following the administration of 2-deoxyglucose 4 suggested that plasma GH concentrations might be elevated in other conditions characterized by impaired intracellular glucose utilization such as uncontrolled diabetes mellitus.Roth and coworkers 5 found the initial plasma GH concentration to be normal in a patient with mild diabetic ketoacidosis. On the other hand, Unger 6 noted

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The Metabolism of Amino Acids in Diabetes Mellitus

Cited by 46 publications

References 12 publications

Metabolomics in diabetes research

Metabolomics in diabetes research

Abnormal amino acid concentrations in plasma and urine of experimentally diabetic dogs

Diabetic Ketosis: Serial Plasma Growth Hormone Concentrations During Therapy

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