PATHOGENESIS OF METABOLIC SYNDROME:
Metabolic syndrome is a cascade of events indicating several
metabolic anomalies occur...
people is found as compared to be lean individuals. Consequently
hyperinsulinemia (high conc. of insulin in plasma) develo...
3. Meanwhile antagonists of insulin i.e. glucagon and
lipases are activated to compensate for energy crisis in
between mea...
6.

A no. of inflammatory cytokines is also released along
with fat such as adipokines –leptin- TNF, IL-6, Resistin
and Ad...
high fat constituents from systemic circulation and fat
component of blood flow to internal organs is
maintained in normal...
high fat constituents from systemic circulation and fat
component of blood flow to internal organs is
maintained in normal...
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Metabolic syndrome

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Transcript of "Metabolic syndrome"

  1. 1. PATHOGENESIS OF METABOLIC SYNDROME: Metabolic syndrome is a cascade of events indicating several metabolic anomalies occurring simultaneously in type II Diabetes Mellitus. Although disturbance in metabolism are also evident in victims of type I Diabetes but the clinical features of metabolic syndrome are associated specifically with type I. Whatever would be the clinical features of the disease, they are either “resulting” from insulin resistivity or are “initiating “ because of it. INSULIN RESISTIVITY: It is described as the gradual loss in the sensitivity of the insulin receptor which is a transmembrane 4 insulin receptor substrate 14 and cytosolic domains of tyrosine kinase (part of 2nd messenger system) .It is to note here that in type I Diabetes - where deficiency of insulin because of the destruction of B cells of Langerhans is present - insulin resistivity does not occur for year and cells respond normally well to intravenous insulin. Abnormal fat constituent in obese and dyslipidemics, understimulation of Glucose and insulin receptor due to sedentary life style and such other contributing risk factors are believed to be responsible for the lost expression of insulin receptors and distortion of signal transduction pathway of insulin in type II Diabetes. Less no. of receptors on cell surface in obese
  2. 2. people is found as compared to be lean individuals. Consequently hyperinsulinemia (high conc. of insulin in plasma) develops which is itself toxic. METABOLIC DISTURBANCES: Normally, when insulin binds to its receptor, phosphorylation of its cytoplasmic tyrosine kinase residues takes place initiating the autophosphorylation of IRS – complexes which activate a variety of enzymes, initiating uptake of glucose and amino acids, glycogenesis, lipogenesis, protein synthesis, gene expression and overall growth like effects. It is also a potent inhibitor of lipases and glucagon. But in insulin resistivity all these functions are reversed. 1. In Liver and Muscle Cells, soon after the meal reduced expression of Glut-receptors and co-transporters due to reduces activity of Glucokinase results in limited intake of glucose and amino acid resulting hyperglycemia. 2. Due to lack of glucose inside the cell , cell does not undergo energy storing processes such as glycogenesis and lipogenesis (reduced activation of glycogen synthase and lipid kinases)
  3. 3. 3. Meanwhile antagonists of insulin i.e. glucagon and lipases are activated to compensate for energy crisis in between meals. Instead of glycolysis, metabolism is shifted towards beta-oxidation of fatty acids which produces accetoacetic acid as a byproduct several times than that of its consumption, which leads to acidosis of liver and muscles resulting decrease in blood PH. This acidosis is corrosive in nature and microalbuminuria and ketonemia develops. 4. Muscle cells undergo wasting and Liver becomes secretory contributing abnormal lipids constituents such as LDL and VLDL in systemic flow resulting dyslipidemia (imbalance in plasma ratios of HDL and LDL) 5. In Adipose tissue, role of insulin is to activate Lipid Kinase and to inhibit hormone-sensitive Lipases. In metabolic syndrome complementary processes start resulting lipolysis. A burst of free fatty acids, TGs, cholesterol from adipocytes into the blood take place and hyperlipidemia (increase in plasma total fat) develops.
  4. 4. 6. A no. of inflammatory cytokines is also released along with fat such as adipokines –leptin- TNF, IL-6, Resistin and Adiponectin into the blood. 7. In almost all cells of the body (except brain cells), insulin interacts with growth hormones and insulin like growth factors synergistically and initiates protein synthesis. But due to revert functions in metabolic syndrome , there is reduction in long-term process of gene expression, DNA synthase activity and repair mechanism (decrease stimulation of P21, RAS, Raf-1, MEK, MAP kinases).Cells become prone to inflammation. A mark) can be noted. 8. Additionally, able increase in prothrombic factors (fibrinogen. Plasminogen activator inhibitor-I), proinflammatory cytokines, CRP (an active acute phase biomarker insulin acts as a vasodilator by secreting eNOS from endothelial cells of vessels. Reduced insulin activity, prothrombic factors and cytokines will cause vasoconstriction and high blood pressure. 9. As a sequel of events atherosclerosis and high risk of CVD develops if not managed. 10. Healthy visceral fat which forms a layer around internal organs is protective in nature such that it absorb
  5. 5. high fat constituents from systemic circulation and fat component of blood flow to internal organs is maintained in normal range. Fat around abdomen is also protective for short term because of the presence of portal system –which shuttles in between Liver and systemic flow. But when insulin sensitivity is lost then at regular intervals under the activation of sympathetic nervous system it secretes high amount of free fatty acids into Liver then in systemic circulation leading to obesity and fat around abdomen. This document is for study purpose, unauthorized copy pasting is forbidden Sara siddiqui References: Text book of Medical physiology by Guyton and Hall 12th edition Harper’s illustrated biochemistry 26th edition
  6. 6. high fat constituents from systemic circulation and fat component of blood flow to internal organs is maintained in normal range. Fat around abdomen is also protective for short term because of the presence of portal system –which shuttles in between Liver and systemic flow. But when insulin sensitivity is lost then at regular intervals under the activation of sympathetic nervous system it secretes high amount of free fatty acids into Liver then in systemic circulation leading to obesity and fat around abdomen. This document is for study purpose, unauthorized copy pasting is forbidden Sara siddiqui References: Text book of Medical physiology by Guyton and Hall 12th edition Harper’s illustrated biochemistry 26th edition

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