diabetestalk.net

Physiological Vs Pathological Insulin Resistance

Insulin Resistance - Physiological Vs. Pathological

Insulin Resistance - Physiological Vs. Pathological

Insulin Resistance - Physiological vs. Pathological Insulin Resistance - Physiological vs. Pathological This a must-read to really understand IR - especially for those living LC/HF. In the article, he links to this study of dolphins, also worth a look. It's amazing how may "studies" you can find even in respectable channels with headlines like "High Fat Diet Causes Insulin Resistance", which are apparently completely ignorant of this distinction. D.D. Family T2, trying to live a healthy life Its all about protecting the almighty brain. The dolphin study would not open. They did a similar study not far from me finding out that dolphins turn IR on and off daily to conserve glucose for thier brains while resting. No Rx, Diet modification, exercise, Supps and Herbals Interesting stuff. There haven't been enough studies done of healthy people in ketosis...what happens to the body, and why. My IR may be more 'pathological'...something isn't working right for me (I guess...there's no outward sign of anything wrong). What about the inflammation in the article Peter cited? I do believe that chronic inflammation is bad for the body. Do other people get the HS-CRP test? My HS-CRP was 3.0 before I started insulin, and jumped up to 6.6 when I was on insulin...according to everything I've read, both readings are too high (the lower the better, with 3.0 being the top of the normal range). I know that insulin is pro-inflammatory, and I hope it's dropped at least back to 3.0 since I stopped insulin. But why, I wonder, is it so high? I've been doing all Denny's 'anti-inflammatory' things for a couple of years. Also, I have to ask (again), if all the fat-burning cells become insulin resistant, and the brain only needs so much glucose, how does the excess glucose get taken out of the bloo Continue reading >>

Frontiers | Pro-angiogenic Role Of Insulin: From Physiology To Pathology | Physiology

Frontiers | Pro-angiogenic Role Of Insulin: From Physiology To Pathology | Physiology

Front. Physiol., 05 April 2017 | Pro-angiogenic Role of Insulin: From Physiology to Pathology 1Group of Investigation in Tumor Angiogenesis, Vascular Physiology Laboratory, Basic Sciences Department, Universidad del Bo Bo, Chilln, Chile 2Group of Research and Innovation in Vascular Health, Department of Basic Sciences, Universidad del Bo-Bo, Chilln, Chile 3Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepcin, Concepcin, Chile 4Department of Physiology, Pontificia Universidad Catlica de Chile, Santiago, Chile 5Department of Urology, Roswell Park Cancer Institute, Buffalo, NY, USA 6Vascular Physiology Laboratory, Department of Physiology, Faculty of Biological Sciences, Universidad of Concepcin, Concepcin, Chile The underlying molecular mechanisms involve in the regulation of the angiogenic process by insulin are not well understood. In this review article, we aim to describe the role of insulin and insulin receptor activation on the control of angiogenesis and how these mechanisms can be deregulated in human diseases. Functional expression of insulin receptors and their signaling pathways has been described on endothelial cells and pericytes, both of the main cells involved in vessel formation and maturation. Consequently, insulin has been shown to regulate endothelial cell migration, proliferation, and in vitro tubular structure formation through binding to its receptors and activation of intracellular phosphorylation cascades. Furthermore, insulin-mediated pro-angiogenic state is potentiated by generation of vascular growth factors, such as the vascular endothelial growth factor, produced by endothelial cells. Additionally, diseases such as insulin resistance, obesity, diabetes, and cancer may be associated with the deregula Continue reading >>

Review Insulin And Insulin-like Growth Factor Receptors In The Brain: Physiological And Pathological Aspects

Review Insulin And Insulin-like Growth Factor Receptors In The Brain: Physiological And Pathological Aspects

1. Introduction: the insulin-IGF system The insulin-like growth factor (IGF) system constitutes a hormonal network comprising ligands, receptors and binding proteins. The ligands, insulin, IGF-1 and IGF-2 (herein named IGF-related peptides), have distinct tissues of expression and separate physiological functions. They generally activate different receptors, though both the insulin receptor (IR) and the Type 1 IGF receptor (IGF-1R), despite major differences in expression patterns, are very similar in both structure and activity in regard to signaling pathways. Insulin is primarily a metabolic hormone functioning on muscle, fat and liver via activation of its cognate receptor, though it also functions on tissues that are not considered classically metabolic, such as the vasculature and the brain. The IGFs have a more mitogenic role both during fetal development and postnatally. The IGFs are important progression factors during the cell cycle and they affect cell survival in adult tissues. In certain cases, IGF-1 and IGF-2 actually demonstrate specific differentiated functions via activation of the IGF-1R, as the IGF-2R does not have signaling capabilities. The IGF-binding proteins (IGFBP1-6) have high affinity for both IGF-1 and IGF-2, protect the IGFs in the circulation and deliver them to the tissues. Hence, IGFBPs׳ main role is to modulate the bioavailability of the ligands. The IGFBPs exhibit numerous biological functions, both via their control of local “free” (unbound) IGFs׳ interactions with cell-surface receptors and, in some cases, in a ligand-independent manner. As opposed to the IGFs, insulin has no similar binding proteins and circulates freely. In this review we will discuss the expression and function of insulin, IGFs and their receptors in the brain Continue reading >>

Physiological/pathological Ramifications Of Transcription Factors In The Unfolded Protein Response

Physiological/pathological Ramifications Of Transcription Factors In The Unfolded Protein Response

Physiological/pathological ramifications of transcription factors in the unfolded protein response 1Soonchunhyang Institute of Medi-Bio Science (SIMS), Soonchunhyang University, Cheonan-si, Choongchungnam-do 31151, Republic of Korea; 2Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, 92307 USA Corresponding authors: rkaufman{at}sbpdiscovery.org, hanjs015{at}sch.ac.kr Numerous environmental, physiological, and pathological insults disrupt protein-folding homeostasis in the endoplasmic reticulum (ER), referred to as ER stress. Eukaryotic cells evolved a set of intracellular signaling pathways, collectively termed the unfolded protein response (UPR), to maintain a productive ER protein-folding environment through reprogramming gene transcription and mRNA translation. The UPR is largely dependent on transcription factors (TFs) that modulate expression of genes involved in many physiological and pathological conditions, including development, metabolism, inflammation, neurodegenerative diseases, and cancer. Here we summarize the current knowledge about these mechanisms, their impact on physiological/pathological processes, and potential therapeutic applications. The endoplasmic reticulum (ER) is the cellular organelle for protein folding and maturation, lipid and sterol biosynthesis, and calcium storage. ER homeostasis is disrupted by a number of insults that cause the accumulation of unfolded or misfolded proteins in the ER lumen, thereby activating the unfolded protein response (UPR) ( Schroder and Kaufman 2005 ; Bernales et al. 2006 ). The UPR has outputs designed to couple the ER protein-folding capacity with demand so that the cell can survive and function. In order to increase protein-folding capacity, the homeost Continue reading >>

Coexistence Of Insulin Resistance And Increased Glucose Tolerance In Pregnant Rats: A Physiological Mechanism For Glucose Maintenance

Coexistence Of Insulin Resistance And Increased Glucose Tolerance In Pregnant Rats: A Physiological Mechanism For Glucose Maintenance

Volume 90, Issues 2122 , 6 June 2012, Pages 831-837 Coexistence of insulin resistance and increased glucose tolerance in pregnant rats: A physiological mechanism for glucose maintenance The contribution of insulin resistance (IR) and glucose tolerance to the maintenance of blood glucose levels in non diabetic pregnant Wistar rats (PWR) was investigated. PWR were submitted to conventional insulin tolerance test (ITT) and glucose tolerance test (GTT) using blood sample collected 0, 10 and 60min after intraperitoneal insulin (1U/kg) or oral (gavage) glucose (1g/kg) administration. Moreover, ITT, GTT and the kinetics of glucose concentration changes in the fed and fasted states were evaluated with a real-time continuous glucose monitoring system (RT-CGMS) technique. Furthermore, the contribution of the liver glucose production was investigated. Conventional ITT and GTT at 0, 7, 14 and 20days of pregnancy revealed increased IR and glucose tolerance after 20days of pregnancy. Thus, this period of pregnancy was used to investigate the kinetics of glucose changes with the RT-CGMS technique. PWR (day 20) exhibited a lower (p<0.05) glucose concentration in the fed state. In addition, we observed IR and increased glucose tolerance in the fed state (PWR-day 20 vs. day 0). Furthermore, our data from glycogenolysis and gluconeogenesis suggested that the liver glucose production did not contribute to these changes in insulin sensitivity and/or glucose tolerance during late pregnancy. In contrast to the general view that IR is a pathological process associated with gestational diabetes, a certain degree of IR may represent an important physiological mechanism for blood glucose maintenance during fasting. Continue reading >>

Physiologic Insulin Therapy, The New Best Practice Part 1

Physiologic Insulin Therapy, The New Best Practice Part 1

Adapted from an Article by Don Zettervell Submitted by Kathy Silliman, RN There has always been a struggle in the management of patients with diabetes. How do we reach A1c goals of less than 7% and at the same time avoid hypoglycemia? Are we allowing fear of hypoglycemia let us get too comfortable with hyperglycemia? Most protocols for managing high blood sugars require contacting prescribers when glucose levels exceed 300 or even 400mg/dl. Since symptomatic hyperglycemia starts at glucose levels of 180mg/dl, allowing blood sugars to elevate to such levels proves the point that we are too comfortable with hyperglycemia. On the other hand, no one would suggest a prescriber be contacted every time blood sugars are above 180mg/dl. There is also the problem of giving sliding scale insulin when blood sugars are deemed too high, especially when it’s being discouraged by AMDA, ADA, AACE and the State Operations Manual. Yet, 84% of patients entering a nursing facility from a hospital setting on sliding scale insulin remain on it for the duration of their stay and more than ½ of all patients using insulin have standing sliding scale orders. So what are we to do? There is a new approach that is rapidly becoming the treatment of choice. It comes from understanding how the body normally handles glucose and then applying those principles to insulin therapy. Simply put, it is physiologic insulin therapy. Since the body’s insulin needs change constantly, this means creating insulin protocols that provide consistent, yet flexible insulin dosing that can mimic normal physiology. This new approach has some very distinct advantages. Dosing flexibility can decrease unnecessary phone calls to prescribers, helps to minimize hypoglycemic episodes and most importantly improves glucose con Continue reading >>

When Insulin Resistance Is A Good Thing

When Insulin Resistance Is A Good Thing

Peter of Hyperlipid has been saying this for a long time. But, alas, Peter is a veterinarian and easily dismissed by those who don't want to look at what he blogs at face value. He constantly uses two terms for IR. Pathological insulin resistance is the kind commonly found at the origins of T2. Related to glucose overload and oxidative stress (which results), it is a pathological condition and not easily reversed. Physiological insulin resistance on the other hand is both a healthy and a transitory condition. It comes about with heavy restriction of carbs and their replacement with fat. Since there is so much less glucose around, the body uses this mechanism to "switch" most cells to other energy source, saving the little glucose available for the few cells which must have it. Here's a great science journal article FINALLY saying what Peter's been saying for years. In the discussion, you can see many of the huge health benefits of a ketogenic diet. They are rebutting a previous study which had good data but erroneous conclusions and citing 9 other studies to back up their case. It is a study I have often seen cited by people who buy the ADA line that diabetics need to eat a low-fat diet. That study established HIGHER insulin resistance on a high-fat (low-carb) diet. It's true, but doesn't mean what they imagined it to mean. What they failed to realize is the difference between temporary IR induced by a LC/HF WOE and pathological IR caused by mitochondrial damage which is a feature of T2. That one is bad, this one is good. It's part of the body switching off glucose onto other fuels - a critical part of addressing T2 with keto dieting. The reason it starts out "to the editor" is because the study which is being rebutted was published in this same journal. There is a lin Continue reading >>

Physiological Insulin Resistance

Physiological Insulin Resistance

Diabetes Forum The Global Diabetes Community Find support, ask questions and share your experiences. Join the community Hi, I have been doing a little reading on this subject but I`m still not sure if I have a handle on it or not and would like a little advice please. My understanding is as follows: A lot of t2`s have Pathological insulin resistance so that when we produce glucose our pancreas has to produce insulin but we don`t use it very well which means more insulin which causes weight gain and so on... A low carb diet produces less glucose which calls for less insulin which has to be a good thing presumably. However, carb restriction can also cause Physiological insulin resistance which, if I understand correctly, saves the smaller amount of glucose which is produced for the brain by making the muscles insulin resistant which leads to higher bg readings. Is my understanding anywhere close to correct and will these higher bg levels lead to a higher HBA1C ? Thank you for reading and please reply with your opinions. Chris. Hi, I have been doing a little reading on this subject but I`m still not sure if I have a handle on it or not and would like a little advice please. My understanding is as follows: A lot of t2`s have Pathological insulin resistance so that when we produce glucose our pancreas has to produce insulin but we don`t use it very well which means more insulin which causes weight gain and so on... A low carb diet produces less glucose which calls for less insulin which has to be a good thing presumably. However, carb restriction can also cause Physiological insulin resistance which, if I understand correctly, saves the smaller amount of glucose which is produced for the brain by making the muscles insulin resistant which leads to higher bg readings. Is my Continue reading >>

Insulin Resistance

Insulin Resistance

Insulin resistance (IR) is a pathological condition in which cells fail to respond normally to the hormone insulin. The body produces insulin when glucose starts to be released into the bloodstream from the digestion of carbohydrates in the diet. Normally this insulin response triggers glucose being taken into body cells, to be used for energy, and inhibits the body from using fat for energy. The concentration of glucose in the blood decreases as a result, staying within the normal range even when a large amount of carbohydrates is consumed. When the body produces insulin under conditions of insulin resistance, the cells are resistant to the insulin and are unable to use it as effectively, leading to high blood sugar. Beta cells in the pancreas subsequently increase their production of insulin, further contributing to a high blood insulin level. This often remains undetected and can contribute to the development of type 2 diabetes or latent autoimmune diabetes of adults.[1] Although this type of chronic insulin resistance is harmful, during acute illness it is actually a well-evolved protective mechanism. Recent investigations have revealed that insulin resistance helps to conserve the brain's glucose supply by preventing muscles from taking up excessive glucose.[2] In theory, insulin resistance should even be strengthened under harsh metabolic conditions such as pregnancy, during which the expanding fetal brain demands more glucose. People who develop type 2 diabetes usually pass through earlier stages of insulin resistance and prediabetes, although those often go undiagnosed. Insulin resistance is a syndrome (a set of signs and symptoms) resulting from reduced insulin activity; it is also part of a larger constellation of symptoms called the metabolic syndrome. Insuli Continue reading >>

Hepatic Insulin Resistance Vs Physiological Insulin Resistance

Hepatic Insulin Resistance Vs Physiological Insulin Resistance

Hepatic Insulin Resistance vs Physiological Insulin Resistance Hepatic Insulin Resistance vs Physiological Insulin Resistance Can anyone explain the difference? I've read Marks article on the Physiological insulin resistance brought about by low carb and as far as I understand thats temporary and reversible, I'm curious as to how that compares to 'hepatic' insulin resistance? Physiological insulin resistance is simply your body reacting to a lack of carbohydrates in your body to spare glucose for your brain. It can be reversed by eating carbohydrates again. Hepatic (and muscular, and adipose) insulin resistance is the result of inflammation, oxidative damage, and lipo/glucotoxicity that leads you down the road to metabolic syndrome. Two different things. Though depending on who you ask, they'll tell you a poor low carb diet can certainly lead to and/or aggravate the latter. I'm not naming names, but Jimmy Moore. Hepatic insulin resistance is insulin resistance of the liver. Physiological insulin resistance is insulin resistance that is considered beneficial, as opposed to pathological insulin resistance, which is considered harmful. The idea of physiological insulin resistance is that is occurs on low-carb diets and serves to conserve carbohydrates, which would be scarce. Pathological insulin resistance can occur on high-carb diets, where insulin and its sensitivity would be important. The distinction you wish to make is between pathological and physiological insulin resistance. A pathology is a disease, whereas anything deemed physiological means that it is within the normal range observed. Physiological insulin resistance occurs when there is a shortage of blood glucose, and adipose tissue is releasing its contents, free fatty acids, to make up for the energy shortfa Continue reading >>

Physiological And Pathological Changes In Glucose Regulate Brain Akt And Glycogen Synthase Kinase-3*

Physiological And Pathological Changes In Glucose Regulate Brain Akt And Glycogen Synthase Kinase-3*

Insulin regulates the phosphorylation and activities of Akt and glycogen synthase kinase-3 (GSK3) in peripheral tissues, but in the brain it is less clear how this signaling pathway is regulated in vivo and whether it is affected by diabetes. We found that Akt and GSK3 are sensitive to glucose, because fasting decreased and glucose administration increased by severalfold the phosphorylation of Akt and GSK3 in the cerebral cortex and hippocampus of non-diabetic mice. Brain Akt and GSK3 phosphorylation also increased after streptozotocin administration (3 days), which increased blood glucose and depleted blood insulin, indicating regulation by glucose availability even with deficient insulin. Changes in Akt and GSK3 phosphorylation and activities in epididymal fat were opposite to those of brain after streptozotocin treatment. Streptozotocin-induced hyperglycemia and increased brain Akt and GSK3 phosphorylation were reversed by lowering blood glucose with insulin administration. Long term hyperglycemia also increased brain Akt and GSK3 phosphorylation, both 4 weeks after streptozotocin and in db/db insulin-resistant mice. Thus, the Akt-GSK3 signaling pathway is regulated in mouse brain in vivo in response to physiological and pathological changes in insulin and glucose. Insulin resistance and diabetes represent increasingly prevalent conditions that involve impaired regulation of glucose production and utilization ( 1 ). Recently much has been learned about insulin resistance in insulin-sensitive peripheral tissues, such as fat and skeletal muscle ( 2 , 3 ). In contrast, little is understood about diabetes-induced changes in insulin-linked signaling activities in the brain even though cognition is often impaired in diabetic subjects ( 4 ), and the brain accounts for 20% Continue reading >>

Mitochondrial Adaptations To Physiological Vs. Pathological Cardiac Hypertrophy

Mitochondrial Adaptations To Physiological Vs. Pathological Cardiac Hypertrophy

Mitochondrial adaptations to physiological vs. pathological cardiac hypertrophy Division of Endocrinology, Metabolism and Diabetes, and Program in Molecular Medicine 15 North 2030 East, Bldg. 533, Rm. 3110B, Salt Lake City, UT 84112 Corresponding author. Tel: +1 801 585 0727, fax: +1 801 585 0701, Email: [email protected] Search for other works by this author on: Cardiovascular Research, Volume 90, Issue 2, 1 May 2011, Pages 234242, E. Dale Abel, Torsten Doenst; Mitochondrial adaptations to physiological vs. pathological cardiac hypertrophy, Cardiovascular Research, Volume 90, Issue 2, 1 May 2011, Pages 234242, Cardiac hypertrophy is a stereotypic response of the heart to increased workload. The nature of the workload increase may vary depending on the stimulus (repetitive, chronic, pressure, or volume overload). If the heart fully adapts to the new loading condition, the hypertrophic response is considered physiological. If the hypertrophic response is associated with the ultimate development of contractile dysfunction and heart failure, the response is considered pathological. Although divergent signalling mechanisms may lead to these distinct patterns of hypertrophy, there is some overlap. Given the close relationship between workload and energy demand, any form of cardiac hypertrophy will impact the energy generation by mitochondria, which are the key organelles for cellular ATP production. Significant changes in the expression of nuclear and mitochondrially encoded transcripts that impact mitochondrial function as well as altered mitochondrial proteome composition and mitochondrial energetics have been described in various forms of cardiac hypertrophy. Here, we review mitochondrial alterations in pathological and physiological hypertrophy. We suggest that mi Continue reading >>

Insulin And Insulin Resistance

Insulin And Insulin Resistance

Go to: Abstract As obesity and diabetes reach epidemic proportions in the developed world, the role of insulin resistance and its consequences are gaining prominence. Understanding the role of insulin in wide-ranging physiological processes and the influences on its synthesis and secretion, alongside its actions from the molecular to the whole body level, has significant implications for much chronic disease seen in Westernised populations today. This review provides an overview of insulin, its history, structure, synthesis, secretion, actions and interactions followed by a discussion of insulin resistance and its associated clinical manifestations. Specific areas of focus include the actions of insulin and manifestations of insulin resistance in specific organs and tissues, physiological, environmental and pharmacological influences on insulin action and insulin resistance as well as clinical syndromes associated with insulin resistance. Clinical and functional measures of insulin resistance are also covered. Despite our incomplete understanding of the compl Continue reading >>

Insulin And Insulin Resistance - The Ultimate Guide

Insulin And Insulin Resistance - The Ultimate Guide

Insulin is an important hormone that controls many processes in the body. However, problems with this hormone are at the heart of many modern health conditions. Sometimes our cells stop responding to insulin like they are supposed to. This condition is termed insulin resistance, and is incredibly common. In fact, a 2002 study showed that 32.2% of the US population may be insulin resistant (1). This number may rise to 70% in obese adult women and over 80% in some patient groups (2, 3). About a third of obese children and teenagers may also have insulin resistance (4). These numbers are scary, but the good news is that insulin resistance can be dramatically improved with simple lifestyle measures. This article explains what insulin resistance is, why you should care and how you can overcome it. Insulin is a hormone secreted by an organ called the pancreas. Its main role is to regulate the amount of nutrients circulating in the bloodstream. Although insulin is mostly implicated in blood sugar management, it also affects fat and protein metabolism. When we eat a meal that contains carbohydrates, the amount of blood sugar in the bloodstream increases. This is sensed by the cells in the pancreas, which then release insulin into the blood. Then insulin travels around the bloodstream, telling the body's cells that they should pick up sugar from the blood. This leads to reduced amounts of sugar in the blood, and puts it where it is intended to go, into the cells for use or storage. This is important, because high amounts of sugar in the blood can have toxic effects, causing severe harm and potentially leading to death if untreated. However, due to various reasons (discussed below), sometimes the cells stop responding to the insulin like they are supposed to. In other words, they Continue reading >>

Physiological Insulin Resistance

Physiological Insulin Resistance

I have been trying to find an answer to why my FBG levels have been increasing over the last couple of weeks. It is very frustrating and as a diabetic trying to reverse the disease it is scary (will this WOE work? Are the consequences of out of control diabetes, I am trying to escape, going to happen anyways?). I ran across a blog post that seems to describe what may be happening in my case. It is a possible phenomenon called Physiological Insulin Resistance. The High Blood Glucose Dilemma on Low Carb (LC) Diets If you are on a ketogenic or very low carb (VLC) diet (e.g. with 50-100gr carb/day and/or eating ketone producing MCT oils such as coconut oil), you m Low insulin levels activate hormone sensitive lipase. Fatty tissue breaks down and releases non-esterified fatty acids (NEFA). These are mostly taken up by muscle cells as fuel and automatically induce insulin resistance in those muscles. Palmitic acid is the primary NEFA released from human adipose tissue during fasting. Think of palmitic as a signal molecule to tell the muscles that inhibition of glucose uptake is needed and to tell the liver that increased gluconeogenesis is required because there is no food coming in. This in turns increases the blood sugar. One of the supporting blog post to the one posted above spoke of person experience.The author, like me, gets a consistent mild ketosis readings. Using Ketostix I am getting a consistent 15 dl reading and at high BG. You need to get calories from somewhere, should it be from carbohydrate or fat? I am going to continue reading/researching down this path to determine the implications. The author of the blogs conclusion was as long as his HbA1c is 4.4% he does not care about the high blood sugar readings. This is one voice so I want to learn more. Has anyone Continue reading >>

More in ketosis