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Metabolic syndrome and type 2 diabetes mellitus: focus on peroxisome proliferator activated receptors (PPAR).

Tenenbaum A, Fisman EZ, Motro M - Cardiovasc Diabetol (2003)

Bottom Line: The main factors characteristic of this syndrome are abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, insulin resistance (with or without glucose intolerance), prothrombotic and proinflammatory states.This pathway leads mainly to the macrovascular complications of metabolic syndrome; 2) with massive damage of pancreatic beta cells leading to progressively decrease of insulin secretion and to hyperglycemia (e.g. overt type 2 diabetes).This pathway leads to both microvascular and macrovascular complications.

View Article: PubMed Central - HTML - PubMed

Affiliation: Cardiac Rehabilitation Institute, Sheba Medical Center, 52621 Tel-Hashomer, Israel. altenen@sheba.health.gov.il

ABSTRACT
The metabolic syndrome is a highly prevalent clinical entity. The recent Adult Treatment Panel (ATP III) guidelines have called specific attention to the importance of targeting the cardiovascular risk factors of the metabolic syndrome as a method of risk reduction therapy. The main factors characteristic of this syndrome are abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, insulin resistance (with or without glucose intolerance), prothrombotic and proinflammatory states. An insulin resistance following nuclear peroxisome proliferator activated receptors (PPAR) deactivation (mainly obesity-related) is the key phase of metabolic syndrome initiation. Afterwards, there are 2 principal pathways of metabolic syndrome development: 1) with preserved pancreatic beta cells function and insulin hypersecretion which can compensate for insulin resistance. This pathway leads mainly to the macrovascular complications of metabolic syndrome; 2) with massive damage of pancreatic beta cells leading to progressively decrease of insulin secretion and to hyperglycemia (e.g. overt type 2 diabetes). This pathway leads to both microvascular and macrovascular complications. We suggest that a PPAR-based appraisal of metabolic syndrome and type 2 diabetes may improve our understanding of these diseases and set a basis for a comprehensive approach in their treatment.

No MeSH data available.


Related in: MedlinePlus

The relationship between metabolic syndrome, insulin resistance, hyperinsulinemia and hyperglycemia (overt type 2 diabetes). An insulin-resistant state following nuclear peroxisome proliferator activated receptors (PPAR) deactivation is the key phase of metabolic syndrome initiation. Afterwards, there are 2 principal pathways of metabolic syndrome development: 1) With preserved pancreatic beta cells function and insulin hypersecretion which can compensate for insulin resistance. This pathway leads mainly to the macrovascular complications of metabolic syndrome; 2) With massive damage of pancreatic beta cells leading to progressively decrease of insulin secretion and to hyperglycemia (e.g. overt type 2 diabetes). This pathway leads both to microvascular and macrovascular complications. Time-related scheme.
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Figure 1: The relationship between metabolic syndrome, insulin resistance, hyperinsulinemia and hyperglycemia (overt type 2 diabetes). An insulin-resistant state following nuclear peroxisome proliferator activated receptors (PPAR) deactivation is the key phase of metabolic syndrome initiation. Afterwards, there are 2 principal pathways of metabolic syndrome development: 1) With preserved pancreatic beta cells function and insulin hypersecretion which can compensate for insulin resistance. This pathway leads mainly to the macrovascular complications of metabolic syndrome; 2) With massive damage of pancreatic beta cells leading to progressively decrease of insulin secretion and to hyperglycemia (e.g. overt type 2 diabetes). This pathway leads both to microvascular and macrovascular complications. Time-related scheme.

Mentions: The factor that dominates in obesity is the permanent elevation of plasma free fatty acid (FFA) and the predominant utilization of lipids by muscles inducing a diminution of glucose uptake and insulin resistance. An insulin-resistant state – as the key phase of metabolic syndrome – constitutes the major risk factor for the development of diabetes mellitus. Hyperinsulinemia appears to be a compensatory mechanism that responds to increased levels of circulating glucose. People who develop type 2 diabetes usually pass through the phases of excessive adipogenesis (obesity), nuclear peroxisome proliferator activated receptors (PPAR) modulation, insulin resistance, hyperinsulinemia, pancreatic beta cells stress and damage leading to progressively decrease of insulin secretion, impaired glucose postprandial and fasting levels [11-14]. Fasting glucose is presumed to remain normal as long as insulin hypersecretion can compensate for insulin resistance. The fall in insulin secretion leading to hyperglicemia occurs as a late phenomenon and, in fact, separates the patients with metabolic syndrome from those with or without overt diabetes (Figure 1).


Metabolic syndrome and type 2 diabetes mellitus: focus on peroxisome proliferator activated receptors (PPAR).

Tenenbaum A, Fisman EZ, Motro M - Cardiovasc Diabetol (2003)

The relationship between metabolic syndrome, insulin resistance, hyperinsulinemia and hyperglycemia (overt type 2 diabetes). An insulin-resistant state following nuclear peroxisome proliferator activated receptors (PPAR) deactivation is the key phase of metabolic syndrome initiation. Afterwards, there are 2 principal pathways of metabolic syndrome development: 1) With preserved pancreatic beta cells function and insulin hypersecretion which can compensate for insulin resistance. This pathway leads mainly to the macrovascular complications of metabolic syndrome; 2) With massive damage of pancreatic beta cells leading to progressively decrease of insulin secretion and to hyperglycemia (e.g. overt type 2 diabetes). This pathway leads both to microvascular and macrovascular complications. Time-related scheme.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC153546&req=5

Figure 1: The relationship between metabolic syndrome, insulin resistance, hyperinsulinemia and hyperglycemia (overt type 2 diabetes). An insulin-resistant state following nuclear peroxisome proliferator activated receptors (PPAR) deactivation is the key phase of metabolic syndrome initiation. Afterwards, there are 2 principal pathways of metabolic syndrome development: 1) With preserved pancreatic beta cells function and insulin hypersecretion which can compensate for insulin resistance. This pathway leads mainly to the macrovascular complications of metabolic syndrome; 2) With massive damage of pancreatic beta cells leading to progressively decrease of insulin secretion and to hyperglycemia (e.g. overt type 2 diabetes). This pathway leads both to microvascular and macrovascular complications. Time-related scheme.
Mentions: The factor that dominates in obesity is the permanent elevation of plasma free fatty acid (FFA) and the predominant utilization of lipids by muscles inducing a diminution of glucose uptake and insulin resistance. An insulin-resistant state – as the key phase of metabolic syndrome – constitutes the major risk factor for the development of diabetes mellitus. Hyperinsulinemia appears to be a compensatory mechanism that responds to increased levels of circulating glucose. People who develop type 2 diabetes usually pass through the phases of excessive adipogenesis (obesity), nuclear peroxisome proliferator activated receptors (PPAR) modulation, insulin resistance, hyperinsulinemia, pancreatic beta cells stress and damage leading to progressively decrease of insulin secretion, impaired glucose postprandial and fasting levels [11-14]. Fasting glucose is presumed to remain normal as long as insulin hypersecretion can compensate for insulin resistance. The fall in insulin secretion leading to hyperglicemia occurs as a late phenomenon and, in fact, separates the patients with metabolic syndrome from those with or without overt diabetes (Figure 1).

Bottom Line: The main factors characteristic of this syndrome are abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, insulin resistance (with or without glucose intolerance), prothrombotic and proinflammatory states.This pathway leads mainly to the macrovascular complications of metabolic syndrome; 2) with massive damage of pancreatic beta cells leading to progressively decrease of insulin secretion and to hyperglycemia (e.g. overt type 2 diabetes).This pathway leads to both microvascular and macrovascular complications.

View Article: PubMed Central - HTML - PubMed

Affiliation: Cardiac Rehabilitation Institute, Sheba Medical Center, 52621 Tel-Hashomer, Israel. altenen@sheba.health.gov.il

ABSTRACT
The metabolic syndrome is a highly prevalent clinical entity. The recent Adult Treatment Panel (ATP III) guidelines have called specific attention to the importance of targeting the cardiovascular risk factors of the metabolic syndrome as a method of risk reduction therapy. The main factors characteristic of this syndrome are abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, insulin resistance (with or without glucose intolerance), prothrombotic and proinflammatory states. An insulin resistance following nuclear peroxisome proliferator activated receptors (PPAR) deactivation (mainly obesity-related) is the key phase of metabolic syndrome initiation. Afterwards, there are 2 principal pathways of metabolic syndrome development: 1) with preserved pancreatic beta cells function and insulin hypersecretion which can compensate for insulin resistance. This pathway leads mainly to the macrovascular complications of metabolic syndrome; 2) with massive damage of pancreatic beta cells leading to progressively decrease of insulin secretion and to hyperglycemia (e.g. overt type 2 diabetes). This pathway leads to both microvascular and macrovascular complications. We suggest that a PPAR-based appraisal of metabolic syndrome and type 2 diabetes may improve our understanding of these diseases and set a basis for a comprehensive approach in their treatment.

No MeSH data available.


Related in: MedlinePlus