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Insulin And Amino Acids

Amino Acids And Their Significance For Diabetes

Amino Acids And Their Significance For Diabetes

Amino acids and their significance for diabetes Diabetics cannot sufficiently utilise carbohydrates such as sugar, which is an important energy source.Insulin plays a significant role here as it is a blood-sugar reducing endogenous hormone and the production of insulin is lower in those affected. Furthermore, the cells in their bodies are not able to properly absorb the insulin that is available. The reason for this is the highly diminished sensitivity of the cells towards insulin. The cell membranes are unable to recognise the hormone and therefore do not absorb enough of it. The consequence of this so-called insulin resistance is that not enough energy is produced in the cells. Moreover, sugar cannot properly be degraded in the blood and therefore accumulates so that the blood sugar level increases. Over the long-term, a constantly elevated blood sugar level can damage the vessels and lead to calcification and typical resulting illnesses such as stroke or heart attack. Diabetes mellitus type 2 is mostly associated with older people, as the insulin sensitivity in the cells decreases with age. A well-received study from 1998 showed that arginine can reduce insulin resistance, meaning in turn that insulin sensitivity can be increased.1 Arginine - an important amino acid for insulin absorption Another study by European researchers showed that the amino acid arginine is of great importance for the sensitivity of the bodys cells towards insulin. Arginine is a precursor of nitrogen oxide, a transmitting substance which has a direct influence on insulin sensitivity. For the study, six type two diabetes patients were split into two groups. Both groups consumed a normal diabetic diet. One of the groups was administered a placebo to be taken three times daily for one month. The Continue reading >>

Insulin

Insulin

This article is about the insulin protein. For uses of insulin in treating diabetes, see insulin (medication). Not to be confused with Inulin. Insulin (from Latin insula, island) is a peptide hormone produced by beta cells of the pancreatic islets, and it is considered to be the main anabolic hormone of the body.[5] It regulates the metabolism of carbohydrates, fats and protein by promoting the absorption of, especially, glucose from the blood into fat, liver and skeletal muscle cells.[6] In these tissues the absorbed glucose is converted into either glycogen via glycogenesis or fats (triglycerides) via lipogenesis, or, in the case of the liver, into both.[6] Glucose production and secretion by the liver is strongly inhibited by high concentrations of insulin in the blood.[7] Circulating insulin also affects the synthesis of proteins in a wide variety of tissues. It is therefore an anabolic hormone, promoting the conversion of small molecules in the blood into large molecules inside the cells. Low insulin levels in the blood have the opposite effect by promoting widespread catabolism, especially of reserve body fat. Beta cells are sensitive to glucose concentrations, also known as blood sugar levels. When the glucose level is high, the beta cells secrete insulin into the blood; when glucose levels are low, secretion of insulin is inhibited.[8] Their neighboring alpha cells, by taking their cues from the beta cells,[8] secrete glucagon into the blood in the opposite manner: increased secretion when blood glucose is low, and decreased secretion when glucose concentrations are high.[6][8] Glucagon, through stimulating the liver to release glucose by glycogenolysis and gluconeogenesis, has the opposite effect of insulin.[6][8] The secretion of insulin and glucagon into the Continue reading >>

High Insulin Combined With Essential Amino Acids Stimulates Skeletal Muscle Mitochondrial Protein Synthesis While Decreasing Insulin Sensitivity In Healthy Humans

High Insulin Combined With Essential Amino Acids Stimulates Skeletal Muscle Mitochondrial Protein Synthesis While Decreasing Insulin Sensitivity In Healthy Humans

High Insulin Combined With Essential Amino Acids Stimulates Skeletal Muscle Mitochondrial Protein Synthesis While Decreasing Insulin Sensitivity in Healthy Humans Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota 55905 Address all correspondence and requests for reprints to: K. Sreekumaran Nair, MD, PhD, Mayo Clinic, 200 First Street Southwest, Joseph 5194, Rochester, MN 55905. E-mail: [email protected] . Received 2014 Jun 23; Accepted 2014 Sep 4. Copyright 2014 by the Endocrine Society This article has been cited by other articles in PMC. Insulin and essential amino acids (EAAs) regulate skeletal muscle protein synthesis, yet their independent effects on mitochondrial protein synthesis (MiPS) and oxidative function remain to be clearly defined. The purpose of this study was to determine the effects of high or low insulin with or without EAAs on MiPS. Thirty participants were randomized to 3 groups of 10 each with each participant studied twice. Study groups comprised (1) low and high insulin, (2) low insulin with and without EAAs, and (3) high insulin with and without EAAs. The study was conducted in an in-patient clinical research unit. Eligible participants were 18 to 45 years old, had a body mass index of <25 kg/m2, and were free of diseases and medications that might impair mitochondrial function. Low (6 U/mL) and high (40 U/mL) insulin levels were maintained by iv insulin infusion during a somatostatin clamp while maintaining euglycemia (4.75.2 mM) and replacing GH and glucagon. The EAA infusion was 5.4% NephrAmine. l-[ring-13C6]Phenylalanine was infused, and muscle needle biopsies were performed. Muscle MiPS, oxidative enzymes, and plasma amino acid metabolites were measured. MiPS and oxidative enzyme activities did not differ between low and high insu Continue reading >>

Payperview: Amino Acid-stimulated Insulin Secretion: The Role Of The Glutamine-glutamate-alpha-ketoglutarate Axis - Karger Publishers

Payperview: Amino Acid-stimulated Insulin Secretion: The Role Of The Glutamine-glutamate-alpha-ketoglutarate Axis - Karger Publishers

I have read the Karger Terms and Conditions and agree. The role of amino acids in the regulation of insulin secretion has received relatively little attention because of the clinical and basic science focus on glucose and, more recently, on fatty acids as the essential determinants of this process. However, early clinical observation in 1950s and recent genetic studies of protein-sensitive hypoglycemia in children with congenital hyperinsulinism have highlighted the important role of amino acids in pancreatic beta-cell physiology and pathophysiology. Mouse models of three of these disorders have been investigated to elucidate the mechanisms of amino acid-stimulated insulin secretion (AASIS), including activating mutations of glutamate dehydrogenase (GDH), inactivating mutations of the ATP-sensitive potassium channel [sulfonylurea receptor 1 (SUR1) and Kir 6.2], and inactivating mutations of short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD). This chapter describes the effects of these mutations on pathways of AASIS, particularly on the steps of glutamine oxidation [glutamine glutamate alpha-ketoglutarate(KG)] and of glutamine synthesis (glutamate glutamine): the Q E alpha-KG axis. The results confirm that leucine-stimulated insulin secretion (LSIS) acts via GDH to drive flux from Q E alpha-KG in GDH hyperinsulinism. A similar mechanism applies in SCHAD hyperinsulinism, apparently due to the loss of an inhibitory protein-protein interaction of SCHAD on GDH. In contrast, AASIS in SUR1 hyperinsulinism appears to act via glutamine amplification of distal cAMP-dependent steps in insulin release. These mechanisms responsible for protein-sensitive hypoglycemia in genetic disorders of insulin secretion are likely also relevant to normal regulation of insulin secretion, where Continue reading >>

The Effect Of Insulin On Amino Acid Metabolism

The Effect Of Insulin On Amino Acid Metabolism

Full text Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.5M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References. These references are in PubMed. This may not be the complete list of references from this article. Articles from Biochemical Journal are provided here courtesy of The Biochemical Society Continue reading >>

Effect Of Amino Acids And Proteins On Insulin Secretion In Man

Effect Of Amino Acids And Proteins On Insulin Secretion In Man

Summary Following the demonstration that administration of leucine accentuates the hypoglycemia of some patients with “idiopathic hypoglycaemia of childhood” (1956) and of some patients with pancreatic islet cell tumours (1959) we initiated studies to explore the mechanism of leucine-induced hypoglycaemia. Sensitivity to leucine-hypoglycaemia can be induced consistently in healthy subjects after administration of sulfonylurea compounds. Increased release of pancreatic insulin is the primary mechanism by which leucine causes a fall in blood glucose in sulfonylurea-induced as well as in naturally occurring leucine hypoglycaemia. Experimentally-induced sensitivity to leucine hypoglycaemia can be used as a model for the further study of leucine hypoglycaemia. Potentiation of insulin activity has not been demonstrated to play a role in the production of leucine-induced hypoglycaemia in man. Leucine induces release of insulin and lowers blood glucose in healthy subjects without prior administration of hypoglycaemic agents, but to a quantitatively lesser extent than in sulfonylurea-induced leucine hypoglycaemia. The more pronounced sensitivity to leucine hypoglycaemia produced experimentally by administration of sulfonylureas and that observed in some patients with “idiopathic hypoglycaemia” or functioning islet cell tumours represents a great exaggeration of what appears to be a normal physiological phenomenon. To determine the effect of leucine on insulin release under physiologic circumstances, protein meals (cooked beef or chicken liver) rich in leucine were fed to healthy subjects. The increases in plasma insulin which resulted from the ingestion of the protein meals were considerably greater than those which would have been expected to have resulted from the mode Continue reading >>

Stimulation Of Insulin Secretion By Amino Acids.

Stimulation Of Insulin Secretion By Amino Acids.

Stimulation of insulin secretion by amino acids. This article has been cited by other articles in PMC. Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.0M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References . These references are in PubMed. This may not be the complete list of references from this article. Floyd JC, Jr, Fajans SS, Conn JW, Knopf RF, Rull J. Insulin secretion in response to protein ingestion. J Clin Invest. 1966 Sep;45(9):14791486. [ PMC free article ] [ PubMed ] Fajans SS, Knopf RF, Floyd JC, Power L, Conn JW. THE EXPERIMENTAL INDUCTION IN MAN OF SENSITIVITY TO LEUCINE HYPOGLYCEMIA. J Clin Invest. 1963 Feb;42(2):216229. [ PMC free article ] [ PubMed ] FLOYD JC, Jr, FAJANS SS, KNOPF RF, CONN JW. EVIDENCE THAT INSULIN RELEASE IS THE MECHANISM FOR EXPERIMENTALLY INDUCED LEUCINE HYPOGLYCEMIA IN MAN. J Clin Invest. 1963 Nov;42:17141719. [ PMC free article ] [ PubMed ] YALOW RS, BERSON SA. Immunoassay of endogenous plasma insulin in man. J Clin Invest. 1960 Jul;39:11571175. [ PMC free article ] [ PubMed ] FAJANS SS, FLOYD JC, Jr, KNOPF RF, CONN JW. A COMPARISON OF LEUCINE- AND ACETOACETATE-INDUCED HYPOGLYCEMIA IN MAN. J Clin Invest. 1964 Oct;43:20032008. [ PMC free article ] [ PubMed ] DOLE VP. A relation between non-esterified fatty acids in plasma and the metabolism of glucose. J Clin Invest. 1956 Feb;35(2):150154. [ PMC free article ] [ PubMed ] Yalow RS, Glick SM, Roth J, Berson SA. Plasma insulin and growth hormone levels in obesity and diabetes. Ann N Y Acad Sci. 1965 Oct 8;131(1):357373. [ PubMed ] YALOW RS, BERSON SA. DYNAMICS OF INSULIN SECRETION IN HYPOGLYCEMIA. Diabetes. 1965 Jun;14:341349. [ PubMed ] KN Continue reading >>

Amino Acid Ingestion Strongly Enhances Insulin Secretion In Patients With Long-term Type 2 Diabetes

Amino Acid Ingestion Strongly Enhances Insulin Secretion In Patients With Long-term Type 2 Diabetes

OBJECTIVE—Insulin secretion in response to carbohydrate intake is blunted in type 2 diabetic patients. However, it is not clear whether the insulin response to other stimuli, such as amino acids, is also diminished. Recently, we defined an optimal insulinoptropic mixture containing free leucine, phenylalanine, and a protein hydrolysate that substantially enhances the insulin response in healthy young subjects when coingested with carbohydrate. In this study, we aimed to investigate the insulinotropic capacity of this mixture in long-term type 2 diabetic patients. RESEARCH DESIGN AND METHODS—Ten type 2 diabetic patients (aged 59.1 ± 2.0 years, BMI 26.5 ± 0.7 kg/m2) and 10 healthy control subjects (58.8 ± 2.1 years, 26.5 ± 0.7 kg/m2) visited our lab twice, during which insulin responses were determined following ingestion of carbohydrate only (CHO) or carbohydrate with the free amino acid/protein mixture (CHO+PRO). All subjects received 0.7 g · kg−1 · h−1 carbohydrate with or without 0.35 g · kg−1 · h−1 of the amino acid/protein mixture. RESULTS—Insulin responses were dramatically increased in the CHO+PRO trial in both the type 2 diabetic and control groups (189 and 114%, respectively) compared with the CHO trial (P < 0.01). Plasma glucose, glucagon, growth hormone, cortisol, IGF-I, and IGF binding protein 3 responses were not different between trials within the 2-h time frame. CONCLUSIONS—The insulin secretory capacity in long-term type 2 diabetic patients is substantially underestimated, as the insulin response following carbohydrate intake can be nearly tripled by coingestion of a free amino acid/protein mixture. Future research should be performed to investigate whether such nutritional interventions can improve postprandial glucose disposal. T Continue reading >>

Physiologic Effects Of Insulin

Physiologic Effects Of Insulin

Stand on a streetcorner and ask people if they know what insulin is, and many will reply, "Doesn't it have something to do with blood sugar?" Indeed, that is correct, but such a response is a bit like saying "Mozart? Wasn't he some kind of a musician?" Insulin is a key player in the control of intermediary metabolism, and the big picture is that it organizes the use of fuels for either storage or oxidation. Through these activities, insulin has profound effects on both carbohydrate and lipid metabolism, and significant influences on protein and mineral metabolism. Consequently, derangements in insulin signalling have widespread and devastating effects on many organs and tissues. The Insulin Receptor and Mechanism of Action Like the receptors for other protein hormones, the receptor for insulin is embedded in the plasma membrane. The insulin receptor is composed of two alpha subunits and two beta subunits linked by disulfide bonds. The alpha chains are entirely extracellular and house insulin binding domains, while the linked beta chains penetrate through the plasma membrane. The insulin receptor is a tyrosine kinase. In other words, it functions as an enzyme that transfers phosphate groups from ATP to tyrosine residues on intracellular target proteins. Binding of insulin to the alpha subunits causes the beta subunits to phosphorylate themselves (autophosphorylation), thus activating the catalytic activity of the receptor. The activated receptor then phosphorylates a number of intracellular proteins, which in turn alters their activity, thereby generating a biological response. Several intracellular proteins have been identified as phosphorylation substrates for the insulin receptor, the best-studied of which is insulin receptor substrate 1 or IRS-1. When IRS-1 is activa Continue reading >>

Plasma Insulin Responses After Ingestion Of Different Amino Acid Or Protein Mixtures With Carbohydrate

Plasma Insulin Responses After Ingestion Of Different Amino Acid Or Protein Mixtures With Carbohydrate

Plasma insulin responses after ingestion of different amino acid or protein mixtures with carbohydrate From the Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Department of Human Biology, Maastricht University, Maastricht, Netherlands, and the Food and Non-Food Analysis Department, TNO Nutrition and Food Research Institute, Zeist, Netherlands. Address reprint requests to LJC van Loon, Department of Human Biology, Maastricht University, PO Box 616, 6200 MD Maastricht, Netherlands. E-mail: [email protected] . Search for other works by this author on: From the Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Department of Human Biology, Maastricht University, Maastricht, Netherlands, and the Food and Non-Food Analysis Department, TNO Nutrition and Food Research Institute, Zeist, Netherlands. Search for other works by this author on: From the Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Department of Human Biology, Maastricht University, Maastricht, Netherlands, and the Food and Non-Food Analysis Department, TNO Nutrition and Food Research Institute, Zeist, Netherlands. Search for other works by this author on: From the Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Department of Human Biology, Maastricht University, Maastricht, Netherlands, and the Food and Non-Food Analysis Department, TNO Nutrition and Food Research Institute, Zeist, Netherlands. Search for other works by this author on: The American Journal of Clinical Nutrition, Volume 72, Issue 1, 1 July 2000, Pages 96105, Luc JC van Loon, Wim HM Saris, Hans Verhagen, Anton JM Wagenmakers; Plasma insulin responses after ingestion of different amino acid or protein mixtures with carbohydrate, The American Journal of Clinical Nutrition, Volum Continue reading >>

3. Amino Acids Stimulate The Release Of Both Glucagon And Insulin

3. Amino Acids Stimulate The Release Of Both Glucagon And Insulin

In a person without diabetes, a rise in blood amino acid concentration (the result of protein metabolism) stimulates the secretion of both glucagon and insulin, so their blood sugar remains stable. But in people with diabetes, the release of glucagon without insulin or with impaired insulin response can cause our blood sugar to rise precipitously several hours after a meal high in protein. The insulin is secreted to stimulate protein synthesis--the uptake of amino acids into muscle cells--making them less available for gluconeogenesis. The glucagon is secreted to stimulate the uptake of amino acids into the cells of the liver for gluconeogenesis. So why are these two hormones battling for opposing uses of the same amino acids? Isn't that non-productive? Actually, the phenomenon serves an important purpose. As you probably know, insulin lowers the blood sugar, while glucagon raises it. In the non-diabetic state, the release of these two opposing hormones ensures that the amino acids are used for protein synthesis (because of the extra insulin) but the blood sugar doesn't drop to dangerously low levels, even if the meal was low in carbohydrate. As a result, blood glucose concentration remains reasonably stable during protein metabolism. The insulin and glucagon essentially cancel each other out in terms of their effect on blood glucose, while the insulin is still able to promote protein synthesis. But in people with diabetes, as I mentioned earlier, the release of glucagon without insulin or with impaired insulin response can cause our blood sugar to rise precipitously several hours after a meal high in protein. This is due not only to the glucagon's directly raising the blood sugar, but also to the fact that in the absence of insulin it increases the amount of the amino Continue reading >>

Insulin Resistance, And What May Contribute To It

Insulin Resistance, And What May Contribute To It

Shutterstock Insulin resistance is an abnormal response to insulin produced either by the pancreas or given as an injection, as evidenced by blood glucose levels in relation to serum insulin. Previous evidence supports the connection between branched-chain amino acids (BCAA) and the development of insulin resistance. In a study published in Nature Medicine, scientists have discovered that 3-hydroxyisobutyrate (3-HIB), one of the intermediate products in the breakdown of the BCAA valine, plays a role in the transport of fatty acids into skeletal muscle cells, which creates fatty muscles — a contributor to insulin resistance. Amino acids are the building blocks of proteins – there are 20 of them all together. There are nine essential amino acids which cannot be made by the body — three of them are BCAAs, leucine, isoleucine, and valine – which account for 35 percent of the essential amino acids in muscle proteins and 40 percent of the preformed amino acids required by mammals. When proteins are digested or broken down, amino acids result. The human body uses amino acids to make proteins to help the body: Break down food Grow Repair body tissue Perform many other body functions Amino acids can also be used as a source of energy — but that's not typical. BCAA have profoundly altered metabolism in insulin resistant conditions or situations where there is insulin deficiency – and it is only recently that their role has been so closely associated with insulin resistance. Insulin resistance is a major pathological feature in individuals with Type-2 diabetes (T2DM) or part of what is known as the metabolic syndrome — an association between abdominal obesity, insulin resistance, cardiovascular disease (T2DM is considered a cardiovascular disease equivalent), high bl Continue reading >>

Effect Of Insulin On Amino Acid Uptake And Protein Turnover In Skeletal Muscle From Septic Ratsevidence For Insulin Resistance Of Protein Breakdown

Effect Of Insulin On Amino Acid Uptake And Protein Turnover In Skeletal Muscle From Septic Ratsevidence For Insulin Resistance Of Protein Breakdown

• We investigated the effect of different concentrations of insulin (0, 10, 1×102, 1×103, 1×104, and 1×105 mU/L [0, 70, 7×102, 7×103, 7×104, and 7×105 pmol/L]) on amino acid (α-aminoisobutyric acid) uptake and protein synthesis and breakdown in incubated extensor digitorum longus (EDL) and soleus muscles of rats. We studied three groups: (1) untreated, fed rats; (2) sham-operated rats; and (3) septic rats. Sepsis was induced by cecal ligation and puncture. The α-aminoisobutyric acid uptake was increased by insulin in all three groups. Protein synthesis was maximally stimulated by 30% to 40% by 1×102 mU/L (7×102 pmol/L) of insulin in all three groups. Protein degradation in soleus muscle was not affected by insulin. In EDL muscles from untreated and sham-operated rats, protein breakdown was reduced by 15% to 20% by 1 × 102 mU/L (7×102 pmol/L) of insulin. In contrast, protein breakdown was not inhibited by insulin in septic EDL muscle until the concentration of the hormone was increased to 1 ×104 mU/L (7×104 pmol/L), at which concentration the hormonal effect was less than half that in nonseptic muscle. The results suggest a postreceptor insulin resistance of protein breakdown in septic muscle, while the response to the hormone of amino acid transport and protein synthesis was not altered in sepsis. (Arch Surg 1987;122:228-233) Continue reading >>

Effects Of Insulin And Glucagon On The Uptake Of Amino Acids From Arterial Blood By Canine Ileum

Effects Of Insulin And Glucagon On The Uptake Of Amino Acids From Arterial Blood By Canine Ileum

Abstract Insulin and glucagon have variable effects in altering arteriovenous differences for amino acids and glucose in liver and muscle. It has not been determined whether these hormones may similarly affect intestine. Acute effects of intraarterial insulin and glucagon were evaluated inin situ, luminally cleansed ileal segments in anesthetized, fasted dogs. Insulin significantly increased the ileal uptake of valine, isoleucine, leucine, tyrosine, threonine, and serine from arterial blood: uptake of these amino acids was approximately doubled 45 min after the end of the insulin infusion. Insulin had no effect on glucose uptake or release. Glucagon decreased ileal glutamate release into mesenteric venous blood 45 min after the end of infusion but the uptake or release of other amino acids and ammonia was not changed. Glucagon did increase mesenteric blood flow acutely and caused a net release of glucose into mesenteric venous blood. The results indicate that insulin and glucagon directly alter metabolism of the ileumin vivo. Continue reading >>

Insulin Resistance Is Associated With Altered Amino Acid Metabolism And Adipose Tissue Dysfunction In Normoglycemic Women

Insulin Resistance Is Associated With Altered Amino Acid Metabolism And Adipose Tissue Dysfunction In Normoglycemic Women

Insulin resistance is associated adiposity, but the mechanisms are not fully understood. In this study, we aimed to identify early metabolic alterations associated with insulin resistance in normoglycemic women with varying degree of adiposity. One-hundred and ten young and middle-aged women were divided into low and high IR groups based on their median HOMA-IR (0.9 ± 0.4 vs. 2.8 ± 1.2). Body composition was assessed using DXA, skeletal muscle and liver fat by proton magnetic resonance spectroscopy, serum metabolites by nuclear magnetic resonance spectroscopy and adipose tissue and skeletal muscle gene expression by microarrays. High HOMA-IR subjects had higher serum branched-chain amino acid concentrations (BCAA) (p < 0.05 for both). Gene expression analysis of subcutaneous adipose tissue revealed significant down-regulation of genes related to BCAA catabolism and mitochondrial energy metabolism and up-regulation of several inflammation-related pathways in high HOMA-IR subjects (p < 0.05 for all), but no differentially expressed genes in skeletal muscle were found. In conclusion, in normoglycemic women insulin resistance was associated with increased serum BCAA concentrations, down-regulation of mitochondrial energy metabolism and increased expression of inflammation-related genes in the adipose tissue. One of the earliest detectable defects in the metabolic continuum leading to type 2 diabetes is insulin resistance1. Impaired glucose homeostasis is associated with obesity2, but the means by which excessive adiposity induces insulin resistance and glucose intolerance remain controversial. Indeed, only about a quarter of the variance of insulin resistance is explained by BMI in the general population3. Studies have shown that increased risk of heart disease is indepen Continue reading >>

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