Maintenance Of Wholebody Glucose And Ffa Homeostasis

In the postabsorptive (fasting) state, energy is derived primarily from the breakdown of endogenous fat stores, whereas hepatic, and, to a lesser extent, renal endogenous glucose production maintains blood glucose levels for utilization by organs such as the brain. Fatty acids derived from lipoprotein breakdown or released as FFAs from adipose tissue are oxidized as the main source of energy (Fig. 1 and Color Plate 2, following p. 34). Postprandially there is a shift toward storage of energy...

Insulin Resistance

Ingestion of high fat diets and development of obesity is associated with increased triglyceride storage at sites other than adipose tissue, including skeletal muscle, the heart, kidney, and liver. These changes are often associated with chronic elevations in circulating free fatty acids and TAG. This has led to the widely accepted notion that obesity-associated tissue dysfunction, including insulin resistance and cell death, is a direct consequence of chronic exposure of tissues to elevated...

Introduction

Type 2 diabetes is a worldwide health crisis. In the U.S., 20.8 million are affected at a cost of 132 billion in 2002 1 , and the numbers will likely continue to increase. The Centers for Disease Control and Prevention estimates there are more than 40 million people in the U.S. with prediabetes. Given that the Diabetes Prevention Program showed an 11 yearly conversion rate of impaired glucose tolerance IGT to diabetes 2 , there could be as many as 4 million new cases each year. Furthermore, the...

Sociocultural Factors

Although much of the focus of research into the etiology of diseases such as diabetes is usually on the biomedical risk factors, and the unraveling of molecular mechanisms, sociocultural factors can also play a major role. The impact of urbanization and westernization has already been referred to above. For many societies the switch from traditional lifestyles to modern, urban lifestyles has altered dietary habits, markedly reduced physical activity, and changed many of the long-established...

Pulsatility Of Ffa Release

Oscillations in lipolysis have been described in omental tissue of dogs 57 . Electrical stimulation of the sympathetic nerve endings stimulates lipolysis and FFA release from adipose tissue, whereas denervation reduces lipolysis. Studies in dogs 57 , and more recently in humans 58 , confirmed that the pulsatility of FFA release is linked to neuronal activity, as 3-receptor blockade partly abrogated FFA and glycerol oscillations. Recently Karpe and colleagues confirmed pulsatility of FFA and...

Effects of FFA on Hepatic Glucose Metabolism

Endogenous glucose production and hepatic insulin resistance are increased in type 2 diabetes 32,129,148 . Elevation of FFAs has been linked to increased HGP in dogs 149 and have been shown to stimulate gluconeo-genesis 145,150 . This has been attributed to an increased intracellular pool of acetylCoA, derived from FFA -oxidation, which can activate pyruvate carboxylase and increase NADH and ATP, which serve as co-factor and source of energy, respectively, for the gluconeogenic pathway. In...

Insulin Resistance Vs Betacell Dysfunction

One of the most controversial issues during the 1980s and 1990s was whether insulin resistance or B-cell dysfunction was the main cause of type 2 diabetes. The fact that persons with type 2 diabetes, and also those with IGT, invariably have both defects fueled the debate. Several highly discussed studies of people at presumed high-risk for type 2 diabetes, but still normoglycemic high risk ethnic groups such as Pima Indians, those with both parents having type 2 diabetes, and women with prior...

Effects of FFA and Islet Triglyceride Stores on Pancreatic Cells Acute Effects of FFAs on Insulin Secretion

Fatty acids exert both acute and long-term effects on insulin secretion. Fatty acids are actively taken up and metabolized by P-cells, and can regulate P-cell enzymes and ion channels 27 . It has long been recognized that FFAs acutely i.e., when elevated for less than about 6 to 12 hours increase glucose-stimulated insulin secretion GSIS 172,178,179 . Conversely, acute lowering of plasma FFAs with nicotinic acid results in a reduction in basal plasma insulin in both nonobese and obese healthy,...

Insulin Hormone Sensitive Lipase Ketoacidosis

Insulin Tissue

I HGP Jglycogenolysis, I gluconeogenesis t Glucose uptake FA esterification I TG lipolysis t Glucose uptake FA esterification I TG lipolysis Fig. 1. Glucose and FFA homeostasis. A. Postabsorptive fasting period Stimulation of adipose tissue lipases, HSL and ATGL, by low plasma insulin concentrations and elevated glucagon, facilitates mobilization of stored triglycerides, releasing fatty acids into the circulation. Low insulin and high glucagon also stimulates gluconeogenesis from FFA and other...

Contemporary Endocrinology

Diagnosis and Management of Pituitary Disorders, edited by B. SWEARINGEN, B.M.K. BlLLER, 2008 Type 2 Diabetes Mellitus An Evidence-Based Approach to Practical Management, edited by Mark N. Feinglos, M. Angelyn Bethel, 2008 Autoimmune Diseases in Endocrinology, edited by Anthony P. Weetman, 2008 Energy Metabolism and Obesity Research and Clinical Applications, edited by Patricia A. Donohoue, 2008 Polycystic Ovary Syndrome Current Controversies, from the Ovary to the Pancreas, edited by Andrea...

Fat Diversion from Adipose to Nonadipose Tissue and Lipotoxicity

Ectopic fat deposition appears when the normal buffering capacity of adipose tissue is impaired or exceeded, especially during postprandial periods, and is characterized by diversion of FFAs from adipose depots and lipid deposition in nonadipose tissue liver, muscle, heart, and pancreatic -cells . It may occur by the following mechanisms 1 increased tissue uptake of chronically elevated FFAs, 2 increased lipogenesis within the tissue or 3 reduced FFA oxidation. Lipid accumulation in liver and...

What is the Pathophysiology of Elevated Plasma FFAs

Adipocyte Lipolysis And Circulatory Ffa

Plasma FFA concentration reflects a balance between release by the intravascular lipolysis of triglyceride-rich lipoproteins and lipolysis of predominantly adipose tissue triglyceride stores and tissue uptake predominantly re-esterified in adipose tissue and liver and oxidized in muscle, heart, and liver . In the postabsorptive state, the systemic FFA concentration is determined largely by the rate of FFA entry into the circulation, but postprandially the rate of uptake esterification,...

Transcriptionbased Mechanisms Of Metabolic Reprogramming In Muscle In Response To Overnutrition

Rat Gastrocnemius Muscle

Understanding of metabolic reprogramming and fuel selection in skeletal muscle under different physiological conditions has deepened as a result of new knowledge about transcription factors that serve as broad metabolic regulators. For example, the family of peroxisome proliferator-activated receptors PPARs are powerful global regulators of metabolism according to nutritional status 59-61 . The three major PPAR subtypes, PPARa, 8, and 7 have distinct tissue distributions that reflect their...

Info

Change in prevalence of diabetes 1981-2000 in Australia 36 . Some of the earliest signs of the modern diabetes epidemic were found in the Pacific islands. The tiny island of Nauru became one of the richest countries in the world on a per capita basis , as its phosphate deposits were mined. The island underwent major environmental changes after destruction of the reef to allow ships to approach the island, resulting in loss of fishing enterprises, and destruction of agricultural land for...

Gan 2006 Om Diabetes

Wild S, Roglic G, Green A, Sicree R, King H. Global Prevalence of Diabetes Estimates for the year 2000 and projections for 2030. Diabetes Care 2004 27 1047-1053. 2. International Diabetes Federation. Diabetes Atlas 3rd ed. 2006, Brussels. 3. Sicree R, Shaw JE, Zimmet PZ. Diabetes and impaired glucose tolerance, in Diabetes Atlas, D. Gan, Editor. 2006, International Diabetes Federation Brussels. 10-149. 4. Aspray TJ, Mugusi F, Rashid S, Whiting D, Edwards R, Alberti KG, et al. Rural and urban...

Effects of FFAs on Hepatic Insulin Clearance

An elevation of circulating FFA experimentally induced by an Intralipid heparin infusion decreases hepatic insulin extraction in vivo in dogs 162 . Hennes et al. 171 showed in humans that Intralipid heparin decreased whole body insulin clearance which includes both hepatic and peripheral insulin extraction during hyperglycemic clamps. We have obtained similar findings in humans 172 but only after prolonged Intralipid heparin infusion. On the contrary, others failed to show changes in hepatic...

Homeostasis And Organ Crosstalk

The ability of the organism to sense energy status and switch between demand for energy substrates in the fasted state and their storage in the postprandial state involves close communication between the organs involved in energy homeostasis, and integration of endocrine hormones, adipocytokines, inflammatory cytokines , metabolic glucose, FFAs, amino acids and intermediary metabolites , and neural signals. Liver, pancreas, brain, muscle, intestine, and adipose tissue are the major organs...