Insulin Resistance and Endothelin: Another Pathway for Renal Injury in Patients With the Cardiometabolic Syndrome?

The cardiometabolic syndrome involves a clustering of metabolic and cardiovascular factors which increase the risk of patients developing both Type 2 Diabetes Mellitus and cardio/cerebrovascular disease. Although the mechanistic underpinnings of this link remain uncertain, key factors include insulin resistance, excess visceral adiposity, atherogenic dyslipidemia, and endothelial dysfunction. Of these, a state of resistance to insulin action in overweight/obese patients appears to be central to the pathophysiologic process. Given the increasing prevalence of obesity-related Type 2 Diabetes, coupled with the fact that cardiovascular disease is the number one cause of mortality in this patient population, a more thorough understanding of the cardiometabolic syndrome and potential options to mitigate its risk is imperative. Inherent in the pathogenesis of insulin resistance is an underlying state of chronic inflammation, at least partly in response to excess adiposity. Within obese adipose tissue, an immunomodulatory shift occurs, involving a preponderance of pro-inflammatory immune cells and cytokines/adipokines, along with antigen presentation by adipocytes. Therefore, various adipokines differentially expressed by obese adipocytes may have a significant effect on cardiometabolism. Clusterin is a molecular chaperone that is widely produced by many tissues throughout the body, but is also preferentially overexpressed by obese compared lean adipocytes and relates strongly to multiple components of the cardiometabolic syndrome. Herein, we summarize the known and potential roles of circulating and adipocyte-specific clusterin in cardiometabolism and discuss potential further investigations to determine if clusterin is a viable target to attenuate both metabolic and cardiovascular disease.

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Renal Injury, Abnormal Vitamin D Metabolism and Bone Homeostasis in Aged Rats With Insulin Resistance or Type 2 Diabetes Mellitus

Journal of Investigative Medicine ◽

10.2310/jim.0b013e31817c4270 ◽

2008 ◽

Vol 56 (6) ◽

pp. 872-877

Author(s):

Huang Chang-Quan ◽

Dong Bi-Rong ◽

Xiao Qian ◽

He Ping ◽

Ding Qun-Fang ◽

...

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Vitamin D ◽

Renal Injury ◽

Urinary Albumin ◽

Bone Homeostasis ◽

Aged Rats ◽

Vitamin D Metabolism ◽

Hydroxyvitamin D

ObjectiveThe study aimed to explore the relationship among renal injury, abnormal vitamin D metabolism, and bone homeostasis in insulin resistance (IR) or type 2 diabetes mellitus (T2DM).Design and MethodsThe animal models of IR, T2DM, and T2DM treated with 1-alpha hydroxyvitamin D (1-α(OH)D) were established on 18-month-old male Wistar rats. Glucose infusion rates (GIR) and levels of urinary albumin (UA), serum 25-hydroxyvitamin D (25-(OH)D), serum 1,25-dihydroxyvitamin D (1,25-(OH)2D), and bone mineral density (BMD) in lumbar vertebrae and femoral bone were measured.ResultsUrinary albumin level in the rats with T2DM significantly increased, and there existed a significant and negative correlation between GIR and UA level in the rats with T2DM or IR. The levels of serum 25-(OH)D in all models were similar. The levels of serum 1,25-(OH)2D and BMD in the rats with IR were significantly higher than those in the rats with T2DM and were lower than those in normal control rats. In the aged rats with T2DM, administration of 1-α(OH)D had no effect on serum 25-(OH)D level although significantly increased the levels of serum 1,25-(OH)2D and BMD. There existed a negative correlation between the levels of serum 1,25-(OH)2D and UA in the rats with T2DM or IR.ConclusionsIn IR or T2DM, abnormal vitamin D metabolism is characterized by 1,25-(OH)2D deficiency and is related to renal injury, and there also existed bone loss. In T2DM, both 1,25-(OH)2D deficiency and bone loss can be reversed by 1-α(OH)D.

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