Possible Impairment of Transcardiac Utilization of Adiponectin in Patients With Type 2 Diabetes

Abstract

OBJECTIVE -Adiponectin, an adipocyte-derived protein, has been suggested to enhance insulin sensitivity and prevent atherosclerosis. Circulating adiponecin levels are reduced in states of insulin resistance such as type 2 diabetes. We examined transcardiac utilization of adiponectin in patients with and without type 2 diabetes. RESEARCH DESIGN AND METHODS-A total of 17 male type 2 diabetic patients and 17 male nondiabetic patients were investigated. Venous blood samples were taken to measure glucose and lipid variables. Blood samples for the measurement of adiponectin were collected simultaneously from the aortic root and coronary sinus. Angiographic semiquantitative stenosis score of coronary artery was also evaluated.RESULTS -The adiponectin levels in both the aortic root and coronary sinus in the diabetic patients were significantly lower than those in the nondiabetic patients. The adiponectin level was significantly lower in the coronary sinus than in the aortic root in the nondiabetic patients, but there was no significant difference between adiponectin levels in the aortic root and coronary sinus in the diabetic patients. The total stenosis score, as an index of severity of coronary artery stenosis, was significantly higher in the diabetic patients than in the nondiabetic patients. The stenosis score was correlated with the degree of transcardiac utilization of adiponectin from the aortic root to coronary sinus in the nondiabetic patients but not in the diabetic patients.CONCLUSIONS -Diabetic patients not only have a decreased adiponectin level in the basal state compared with nondiabetic patients but also have impaired utilization of adiponectin in the coronary artery and/or the heart, which may promote the development of atherosclerosis. Diabetes Care 27:2217-2221, 2004A dipose tissue was once thought to be simply a reservoir for energy storage in the form of triglyceride. However, it is now known that adipocytes secrete a variety of proteins, such as tumor necrosis factor (TNF)-␣, plasminogen activator inhibitor-1, leptin, resistin, and adiponectin. These proteins are thought to be involved in a wide range of biological effects. Adiponectin, an adipocyte-derived protein referred to as Acrp30, apM1, AdipoQ, and GBP28, has been independently identified and characterized by several groups (1-5). In humans, adiponectin is one of the most abundant gene transcript proteins in adipocytes, accounting for 0.01% of all proteins (2). In contrast with other adipocyte-derived proteins, the circulating adiponectin level is reduced in patients with coronary artery disease and in states of insulin resistance such as obesity and type 2 diabetes (6 -8). We have previously shown that hypoadiponectinemia is related to insulin resistance in essential hypertension (9). Animal experiments have also suggested that adiponectin enhances insulin sensitivity and prevents atherosclerosis (10,11).It has also been suggested that adiponectin modulates endothelial function and has an inhibitory effect on vascular smooth muscle cell pro...

Adiponectin, T-cadherin and Tumour Necrosis Factor-α in Damaged Cardiomyocytes from Autopsy Specimens

“…13 Possible utilization of adiponectin in the coronary artery and/or heart has been described for non-diabetic patients based on a transcardiac gradient of adiponectin levels from aortic root to coronary sinus. 14 It is interesting that immunostaining for adiponectin was observed at the periphery of damaged cardiomyocytes in lesions at the granulative stage obtained from autopsied hearts with infarction. 15 In another immunohistochemical analysis, the boundaries of mouse hepatocytes were positive for adiponectin after 3 -6 h of carbon tetrachloride treatment, and the cytoplasm was intensely stained after 18 h of treatment.…”

Low Adiponectin Level in Young Normotensive Men with a Family History of Essential Hypertension

“…In contrast with other adipocyte-derived proteins, the circulating adiponectin level is reduced in patients with coronary artery disease and in states of insulin resistance such as obesity and type 2 diabetes (6−8). It has also been suggested that patients with type 2 diabetes not only have a decreased adiponectin level in the basal state but also impaired utilization of adiponectin in the tissue (9). Moreover, we have previously shown that hypoadiponectinemia is related to insulin resistance in essential hypertension, and that blockade of the renin-angiotensin system increases adiponectin levels with improvement in insulin sensitivity, at least in part via a decrease in adipocyte size (10,11).…”

Relationship between Metabolic Syndrome and Early Stage Coronary Atherosclerosis

“…Actually, hypoadiponectinemia is considered as the cause of clustering of MS components through insulin resistance 49) and hypoadiponectinemia is known to be a useful marker of the pathogenesis of MS 18) . Furuhashi M et al 50) reported that decreased adiponectin concentration in coronary blood flow, estimated by simultaneous measurement of the aortic root and coronary sinus, reflected the severity of angiographical coronary atherosclerosis. This suggests that a high concentration of adiponectin exists in coronary blood flow, and adiponectin directly resists the progression of coronary atherosclerosis.…”