Protein Catabolism In Diabetes

Metabolic Pathways - Metabolism And Hormones - Diapedia, The Living Textbook Of Diabetes

There are three groups of molecules that form the core building blocks and fuel substrates in the body: carbohydrates (glucose and other sugars); proteins and their constituent amino acids; and lipids and their constituent fatty acids. The biochemical processes that allow these molecules to be synthesized and stored (anabolism) or broken down to generate energy (catabolism) are referred to as metabolic pathways. Glucose metabolism involves the anabolic pathways of gluconeogenesis and glycogenesis, and the catabolic pathways of glycogenolysis and glycolysis. Lipid metabolism involves the anabolic pathways of fatty acid synthesis and lipogenesis and the catabolic pathways of lipolysis and fatty acid oxidation. Protein metabolism involves the anabolic pathways of amino acid synthesis and protein synthesis and the catabolic pathways of proteolysis and amino acid oxidation. Under conditions when glucose levels inside the cell are low (such as fasting, sustained exercise, starvation or diabetes), lipid and protein catabolism includes the synthesis (ketogenesis) and utilization (ketolysis) of ketone bodies. The end products of glycolysis, fatty acid oxidation, amino acid oxidation and ketone body degradation can be oxidised to carbon dioxide and water via the sequential actions of the tricarboxylic acid cycle and oxidative phosphorylation, generating many molecules of the high energy substrate adenosine triphosphate (ATP). The interplay between glucose metabolism, lipid metabolism, ketone body metabolism and protein and amino acid metabolism is summarized in Figure 1. Amino acids can be a source of glucose synthesis as well as energy production and excess glucose that is not required for energy production can be stored as glycogen or metabolized to acetyl CoA and stored as fa Continue reading >>

Academic Onefile - Document - Diabetes And Protein Metabolism

Listen Larger documents may require additional load time. Copyright: COPYRIGHT 2008 American Diabetes Association The celebrated Greek physician Aretaeus the Cappadocian some 1900years ago described diabetes as a condition with "a melting down of theflesh and limbs into urine." Remarkably, his observations are amazinglydurable and accurate even by the standards of today with reference to type 1diabetes. For example, insulin deprivation in type 1 diabetic patients causesa profound increase in catabolism, especially in skeletal muscle (1-4).Moreover, this net muscle protein catabolism is due to a net increase inprotein breakdown rather than a decline in protein synthesis (1-4). Incontrast, despite substantial alterations in glucose and lipid metabolism,the effect of type 2 diabetes on changes in protein metabolism is at bestsubtle, and results are inconsistent (5-8). A key difference is that in type1 diabetic patients on insulin deprivation, muscle mass withers away (asdemonstrated by profound cachexia in type 1 diabetic patients during thepreinsulin era), whereas no such dramatic changes occur in type 2 diabeticpatients with poor glycemic control. Withdrawal of treatment for 10 days intype 2 diabetic patients had little effect on amino acid levels or proteinmetabolism (8), although glucose metabolism is substantially altered; thismay relate to differences in portal insulin-to-glucagon ratios. Moreover, thedifferences in insulin levels between type 2 diabetic patients andnondiabetic control subjects are not substantial as opposed to the effect ofinsulin deprivation in type 1 diabetic patients. In the current issue, Pereira et al. (9) report results from anextensive study to define whole-body protein metabolism in type 2 diabetes.The authors have studied basal postabsorpt Continue reading >>

Type 2 Diabetes Mellitus And The Catabolic Response To Surgery | Anesthesiology | Asa Publications

Type 2 Diabetes Mellitus and the Catabolic Response to Surgery * Assistant Professor, Biochemist, # Resident, ** Professor, Department of Anesthesia, Assistant Professor, Nutrition and Food Science Center, Associate Professor, School of Dietetics and Human Nutrition, McGill University, Montreal, Canada. Assistant Professor, Department of Anesthesia and Intensive Care Medicine, Philipps-University Marburg, Germany. Clinical Science / Endocrine and Metabolic Systems Type 2 Diabetes Mellitus and the Catabolic Response to Surgery Anesthesiology 2 2005, Vol.102, 320-326. doi: Anesthesiology 2 2005, Vol.102, 320-326. doi: Thomas Schricker, Rejeanne Gougeon, Leopold Eberhart, Linda Wykes, Louise Mazza, George Carvalho, Franco Carli; Type 2 Diabetes Mellitus and the Catabolic Response to Surgery. Anesthesiology 2005;102(2):320-326. 2018 American Society of Anesthesiologists Type 2 Diabetes Mellitus and the Catabolic Response to Surgery You will receive an email whenever this article is corrected, updated, or cited in the literature. You can manage this and all other alerts in My Account THE endocrine response to surgical tissue trauma is characterized by the activation of the hypothalamopituitary and sympathoadrenergic system, resulting in increased circulating concentrations of cortisol, glucagon, epinephrine, and norepinephrine. 1 All these hormones inhibit insulin secretion and/or counteract the peripheral action of insulin, leading to a state of impaired tissue insulin sensitivity. 2,3 Insulin resistance is thought to be one of the principal mechanisms responsible for the catabolic responses to surgery, including stimulated amino acid oxidation, muscle proteolysis, and gluconeogenesis along with decreased glucose utilization and hyperglycemia. 4,5 The similarity between th Continue reading >>

Amino Acid And Protein Metabolism In Diabetes Mellitus

Amino Acid and Protein Metabolism in Diabetes Mellitus In normal man, the fasting state is characterized by release of alanine and glutamine from muscle and in situ muscle catabolism of branched chain amino acids (leucine, isoleucine, and valine). The alanine released by muscle is utilized by the liver for gluconeogenesis. Muscle nitrogen repletion occurs during protein feeding primarily by means of selective hepatic escape and muscle uptake of branched chain amino acids in ingested protein. In the diabetic, amino acid catabolism is exaggerated in the fasting state as reflected by increased uptake of alanine by the liver for gluconeogenesis and accelerated branched chain amino acid catabolism in muscle. After protein feeding, uptake of branched chain amino acids by muscle is reduced and these amino acids accumulate in increased amounts in arterial blood. Protein feeding also exaggerates the hyperglycemia of diabetes by causing an increase in hepatic glucose production. Diabetes is thus characterized by accelerated protein catabolism during fasting as well as diminished nitrogen repletion and hyperglycemia after protein feeding. The hyperketonemia of diabetes may however, have a restraining influence on protein catabolism thereby reducing alanine availability for gluconeogenesis. Continue reading >>

Diabetes Mellitus

diabetes: “marching through”—urine is produced incessantly mellitus: honey-sweet—as opposed to diabetes insipidus (insipid—without flavor) What does the adjective tell us about a traditional method of diagnosis? The traditional method of diagnosis was exactly as suggested by this nomenclature. It was effective, though not quantitative. For those of you who aspire to a career in medicine, it may be comforting to know that it is no longer in use.83 Form Cause type 1 lack of insulin due to destruction of β-cells in pancreas islets type 2 lack of functional response to insulin secondary excess activity of hormones antagonistic to insulin Type 1 diabetes is the form typically observed in the young, whereas the type 2 is more frequent overall and is typically observed in the elderly. MODY—maturity type onset diabetes of the young—is type 2 diabetes in young people. The causation of diabetes type 1 is well understood: it arises from an immunological cross-reaction that destroys the insulin-producing β-cells of the pancreatic islets, which causes a lack of insulin. In contrast, type 2 diabetics may secrete normal, sometimes even increased amounts of insulin. The hormone also binds to its receptors on the cells in the body, which however fail to respond adequately to this stimulus. In spite of substantial research efforts over several decades, we still don’t clearly understand the reasons for this lacking functional response. Secondary, or symptomatic, diabetes is diverse. A straightforward example is the excessive secretion of glucagon by a glucagonoma, that is, a benign tumor derived from glucagon-secreting α-cells in pancreatic islets. More commonly, though, secondary diabetes is caused by treatment with high dosages of glucocorticoid hormones in the treatm Continue reading >>

Protein Metabolism In Diabetes Mellitus

Volume 10, Issue 4 , October 1996, Pages 589-601 Author links open overlay panel Haitham S.Abu-Lebdeh K.SreekumaranNair Get rights and content Insulin deficiency is a protein catabolic state. In vivo studies have shown that insulin enhances short-side-chain amino acid intracellular uptake, stimulates transcription and translation of RNA, increases the gene expression of albumin and other proteins and inhibits liver protein breakdown enzymes. In IDDM patients most of the whole-body protein turnover studies have shown that insulin deficiency increases protein breakdown and increases amino acid oxidation and that these effects are reversed by insulin treatment. Recent studies have demonstrated that a substantial increase in leucine transamination during insulin deprivation contributes to leucine catabolism in IDDM patients. Protein synthesis in the insulin-deprived state is also increased although to a lesser extent than protein breakdown, and this increased whole-body protein synthesis is reduced with an insulin infusion; thus the effects of insulin are largely mediated through its effects on protein breakdown. The metabolic derangements in diabetes frequently involve disturbances in substrates and hormones other than insulin. The observed effects of insulin deficiency in diabetic patients vary in different body compartments; most of the effects of insulin on protein synthesis appear to occur in non-muscular tissues especially in the splanchnic area. In addition, insulin has a differential effect on hepatic protein synthesis, i.e. inhibits fibrinogen synthesis and promotes albumin synthesis. Insulin's anticatabolic effect in IDDM patients is largely due to its inhibition of protein breakdown. The net protein anabolism due to insulin occurs largely in skeletal muscle. In Continue reading >>

The Effect Of Oral Leucine On Protein Metabolism In Adolescents With Type 1 Diabetes Mellitus

International Journal of Pediatric Endocrinology International Journal of Pediatric Endocrinology20102010:493258 Lack of insulin results in a catabolic state in subjects with insulin-dependent diabetes mellitus which is reversed by insulin treatment. Amino acid supply, especially branched chain amino acids such as leucine, enhances protein synthesis in both animal and human studies. This small study was undertaken to assess the acute effect of supplemental leucine on protein metabolism in adolescents with type 1 diabetes. L-[1-13C] Leucine was used to assess whole-body protein metabolism in six adolescent females (1618 yrs) with type 1 diabetes during consumption of a basal diet (containing 58 moles leucine/kg/h) and the basal diet with supplemental leucine (232 moles leucine/kg/h). Net leucine balance was significantly higher with supplemental leucine ( moles leucine/kg body weight/hr) than with the basal diet ( moles leucine/kg body weight/hr) compared to the basal diet ( LeucineBasal DietMuscle Protein SynthesisAnabolic EffectSupplemental Leucine Whole body protein catabolism results when the rate at which body protein is synthesized is less than the rate at which body protein is degraded. Insulin is among the many factors which regulate body protein metabolism. The lack of insulin associated with type 1 diabetes results in the loss of body protein, and insulin treatment reverses the loss of body protein resulting in increased lean body mass [ 1 ]. Several animal studies have demonstrated the importance of insulin in regulating the rate of protein synthesis particularly in muscle tissue (e.g., [ 2 7 ]). In contrast, studies of whole-body protein metabolism in adult humans with type 1 diabetes [ 8 13 ] and prepubertal children [ 14 ] have suggested that the primary e Continue reading >>

Insulin And Protein Metabolism

10.1002/cphy.cp070224 Source: Supplement 21: Handbook of Physiology, The Endocrine System, The Endocrine Pancreas and Regulation of Metabolism Originally published: 2001 Abstract The sections in this article are: 1 Molecular Basis of Insulin Action on Protein Metabolism 2 Physiological Effects of Insulin at the Whole‐Body Level 3 Effects of Insulin on Muscle Tissue 4 Physiological Effects of Insulin on Other Tissues 5 Effect of Insulin on Transport in vivo 6 Insulin Resistance 8 Conclusion Continue reading >>

Cardiac Muscle Protein Catabolism In Dbdb Obese Mice, A Type Ii Diabetes Mellitus Model

Muscle wasting (skeletal and cardiac) is associated with increasing morbidity and mortality. Muscle wasting is primarily the result of increased proteolysis within muscle that leads to excessive degradation of structural proteins such as actin. Accelerated muscle protein degradation is associated with insulin resistance. Muscle protein metabolism in cardiac muscle under conditions of insulin resistance has been understudied. In the current study, we measured protein degradation in cardiac muscle of db/db obese mice. Insulin resistance increased degradation of both soluble and the myofibrillar protein. Insulin/IGF-1 signaling pathways regulate cardiac muscle proteolysis. In the heart muscles from db/db mice, we found that Insulin Receptor Substrate-1 (IRS-1) tyrosine phosphorylation and Akt phosphorylation were decreased causing decreased insulin signaling, and transcription factors FoxO 1 and 3 are dephosphorylated (activated) leading to increased protein degradation. Expression of E3 ubiquitin mRNAs and chymotrypsin-like activity of the proteasome were increased, indicating that the ubiquitin-proteasome system was activated in obese mouse heart. Cardiac muscle protein catabolism was associated with increased serum free fatty acid and inflammatory cytokines in heart, as well as decreased plasma levels of adiponectin. In our previous study, we showed that a decrease in adiponectin and increase in free fatty acid could cause insulin resistance and muscle proteolysis. In this study, we conclude that insulin resistance (resulting from reduced IRS-1/Akt signaling), associated with activation of the ubiquitin-proteasome proteolytic pathway, results in accelerated proteolysis in obese cardiac muscle. Loss of protein stores and a decline in lean body mass are associated with i Continue reading >>

Protein And Energy Metabolism In Type 1 Diabetes

ObjectivesExtracts of parts Musa spp. have been used for the treatment of various diseases in traditional medicine. Studies have shown that these extracts have hypoglycaemic properties. The aim of this work was to gather evidence on the antidiabetic effects of Musa spp. inflorescence.MethodsA systematic review was conducted with searches in three electronic databases, along with manual searches. Studies evaluating the antidiabetic properties of extracts of flower or bract of the genus Musa (in vitro or in vivo) were included.Key findingsOverall, 16 studies were found. The reported assays were of hypoglycaemic effects, oral glucose tolerance, inhibitory activities in carbohydrate metabolism and digestive enzymes, enhanced glucose uptake activity and popular use of the extract in patients with diabetes type 2. In vitro studies showed that use of the extract was associated with antidiabetic effects (e.g. increased glucose uptake and inhibition of carbohydrate digestion enzymes). In induced diabetic models, Musa spp. extracts showed dosedependent glycaemic level reductions compared with pharmacological drugs (P < 0.05).SummaryIn general, promising results regarding antidiabetic activity were found for inflorescence of Musa spp., suggesting that this plant could represent a natural alternative therapy for treating diabetes mellitus type 2. There has been an alarming increase in the prevalence of obesity in people with type 1 diabetes in recent years. Although obesity has long been recognized as a major risk factor for the development of type 2 diabetes and a catalyst for complications, much less is known about the role of obesity in the initiation and pathogenesis of type 1 diabetes. Emerging evidence suggests that obesity contributes to insulin resistance, dyslipidemia and Continue reading >>

Protein Metabolism In Insulin-dependent Diabetes Mellitus

Protein Metabolism in Insulin-Dependent Diabetes Mellitus Endocrine Research Unit, Mayo Clinic and Foundation, Rochester, MN To whom correspondence should be addressed: Mayo Clinic and Foundation, Eisenberg 3-G, 200 First Street S. W., Rochester, MN 55905. Search for other works by this author on: Endocrine Research Unit, Mayo Clinic and Foundation, Rochester, MN Search for other works by this author on: The Journal of Nutrition, Volume 128, Issue 2, 1 February 1998, Pages 323S327S, Michael Charlton, K. Sreekumaran Nair; Protein Metabolism in Insulin-Dependent Diabetes Mellitus, The Journal of Nutrition, Volume 128, Issue 2, 1 February 1998, Pages 323S327S, Patients with insulin-dependent diabetes are in a catabolic state without insulin replacement. The mechanism of insulin's anticatabolic effect has been investigated in whole-body and regional tracer kinetic studies. Whole-body studies have demonstrated that there are increases in both protein breakdown and protein synthesis during insulin deprivation. Because the magnitude of the increase in protein breakdown is greater than the magnitude of the increase in protein synthesis, there is a net protein loss during insulin deprivation. Regional studies have shown that insulin replacement inhibits protein breakdown and synthesis in splanchnic tissue but only inhibits protein breakdown in skeletal muscle. Because the increase in protein synthesis in splanchnic tissues is greater than the increase in protein breakdown, insulin deprivation results in a net accretion of protein in the splanchnic bed. In contrast, in skeletal muscle, there is a net increase in protein breakdown during insulin deprivation, resulting in a net release of amino acids. There are no human data concerning the site of protein accretion in the splanchn Continue reading >>

Protein Controversies In Diabetes

Diabetes SpectrumVolume 13 Number 3, 2000, Page 132 Marion J. Franz, MS, RD, LD, CDE In Brief People with diabetes are frequently given advice about protein that has no scientific basis. In addition, although weight is lost when individuals follow a low-carbohydrate, high-protein diet, there is no evidence that such diets are followed long-term or that there is less recidivism than with other low-calorie diets. People with type 1 or type 2 diabetes who are in poor metabolic control may have increased protein requirements. However, the usual amount of protein consumed by people with diabetes adequately compensates for the increased protein catabolism. People with diabetes need adequate and accurate information about protein on which to base their food decisions. In the United States, ~16% of the average adult consumption of calories is from protein, and this has varied little from 1909 to the present.1 Protein intake is also fairly consistent across all ages from infancy to older age. A daily intake of 2,500 calories contributes ~100 g of protein—about twice what is needed to replace protein lost on a daily basis. Excess amino acids must be converted into other storage products or oxidized as fuel. Therefore, in theory, the excess ingested protein could, through the process of gluconeogenesis, produce glucose. This would mean that 100 g of protein could produce ~50 g of glucose. This has been the basis of the statement that if about half of ingested protein is converted to glucose, protein will have one-half the effect of carbohydrate on blood glucose levels. However, this belief has been challenged.2-4 Protein controversies exist either because research has not provided conclusive answers or because professionals are not aware of the research. This article will review Continue reading >>

Protein Metabolism In Diabetes Mellitus.

Insulin deficiency is a protein catabolic state. In vivo studies have shown that insulin enhances short-side-chain amino acid intracellular uptake, stimulates transcription and translation of RNA, increases the gene expression of albumin and other proteins and inhibits liver protein breakdown enzymes. In IDDM patients most of the whole-body protein turnover studies have shown that insulin deficiency increases protein breakdown and increases amino acid oxidation and that these effects are reversed by insulin treatment. Recent studies have demonstrated that a substantial increase in leucine transamination during insulin deprivation contributes to leucine catabolism in IDDM patients. Protein synthesis in the insulin-deprived state is also increased although to a lesser extent than protein breakdown, and this increased whole-body protein synthesis is reduced with an insulin infusion; thus the effects of insulin are largely mediated through its effects on protein breakdown. The metabolic derangements in diabetes frequently involve disturbances in substrates and hormones other than insulin. The observed effects of insulin deficiency in diabetic patients vary in different body compartments; most of the effects of insulin on protein synthesis appear to occur in non-muscular tissues especially in the splanchnic area. In addition, insulin has a differential effect on hepatic protein synthesis, i.e. inhibits fibrinogen synthesis and promotes albumin synthesis. Insulin's anticatabolic effect in IDDM patients is largely due to its inhibition of protein breakdown. The net protein anabolism due to insulin occurs largely in skeletal muscle. In patients with NIDDM these effects are not noted, presumably because of residual endogenous insulin secretion. In fact, treatments that result i Continue reading >>

Jci Insight -systemic Inflammation Is Associated With Exaggerated Skeletal Muscle Protein Catabolism In Maintenance Hemodialysis Patients

Clinical Medicine Metabolism Nephrology Free access | 10.1172/jci.insight.95185 Systemic inflammation is associated with exaggerated skeletal muscle protein catabolism in maintenance hemodialysis patients 1Division of Nephrology, Vanderbilt University Medical Center (VUMC), Nashville, Tennessee, USA. 2CSRD&D, Veterans Administration Tennessee Valley Healthcare System, Nashville, Tennessee, USA. 5Department of Biostatistics, VUMC, Nashville, Tennessee, USA. 6Selzman Institute for Kidney Health, Baylor College of Medicine, Department of Medicine, Houston, Texas, USA. 7Department of Surgery, VUMC, Nashville, Tennessee, USA. Address correspondence to: T. Alp Ikizler, Vanderbilt University Medical Center, 1161 21st Avenue South & Garland, Division of Nephrology, S-3223 MCN, Nashville, Tennessee 37232-2372, USA. Phone: 615.343.2220; Email: [email protected] . Find articles by Deger, S. in: JCI | PubMed | Google Scholar 1Division of Nephrology, Vanderbilt University Medical Center (VUMC), Nashville, Tennessee, USA. 2CSRD&D, Veterans Administration Tennessee Valley Healthcare System, Nashville, Tennessee, USA. 5Department of Biostatistics, VUMC, Nashville, Tennessee, USA. 6Selzman Institute for Kidney Health, Baylor College of Medicine, Department of Medicine, Houston, Texas, USA. 7Department of Surgery, VUMC, Nashville, Tennessee, USA. Address correspondence to: T. Alp Ikizler, Vanderbilt University Medical Center, 1161 21st Avenue South & Garland, Division of Nephrology, S-3223 MCN, Nashville, Tennessee 37232-2372, USA. Phone: 615.343.2220; Email: [email protected] . Find articles by Hung, A. in: JCI | PubMed | Google Scholar 1Division of Nephrology, Vanderbilt University Medical Center (VUMC), Nashville, Tennessee, USA. 2CSRD&D, Veterans Administration Ten Continue reading >>

Amino Acid And Protein Metabolism In Diabetes Mellitus.

Amino acid and protein metabolism in diabetes mellitus. Felig P , Wahren J , Sherwin R , Palaiologos G . In normal man, the fasting state is characterized by release of alanine and glutamine from muscle and in situ muscle catabolism of branched chain amino acids (lecucine, isoleucine, and valine). The alanine released by muscle is utilized by the liver for gluconeogenesis. Muscle nitrogen repletion occurs during protein feeding primarily by means of selective hepatic escape and muscle uptake of branched chain amino acids in ingested protein. In the diabetic, amino acid catabolism is exaggerated in the fasting state as reflected by increased uptake of alanine by the liver for gluconeogenesis and accelerated branched chain amino acid catabolism in muscle. After protein feeding, uptake of branched chain amino acids by muscle is reduced and these amino acids accumulate in increased amounts in arterial blood. Protein feeding also exaggerates the hyperglycemia of diabetes by causing an increase in hepatic glucose production. Diabetes is thus characterized by accelerated protein catabolism during fasting as well as diminished nitrogen repletion and hyperglycemia after protein feeding. The hyperketonemia of diabetes may however, have a restraining influence on protein catabolism thereby reducing alanine availability for gluconeogenesis. Continue reading >>