Rosiglitazone improves insulin sensitivity, glucose tolerance and ambulatory blood pressure in subjects with impaired glucose tolerance

Bennett, S. M. A.; Agrawal, Ajai; Elasha, H; Heise, Mark; Jones, NigelP.; Walker, Mark; Wilding, John

doi:10.1111/j.1464-5491.2004.01155.x

Cited by 67 publications

(54 citation statements)

References 35 publications

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“…[12][13][14][15][16] RSG has been shown to reduce oxidative stress, thus ameliorating endothelial dysfunction and improving blood vessel elasticity. 31 However, no study to date has examined the effects of RSG on the RAS in human adipocytes and obesity-associated hypertension.…”

Section: Discussionmentioning

confidence: 99%

“…We then proceeded to determine the effect of TNF-␣ on AGT protein expression and Ang II secretion, to elucidate a potential pathway for insulin leading to obesity-associated hypertension through its effects on adipose tissue. Lastly, because the insulin sensitizer rosiglitazone (RSG) has been shown to lower blood pressure in animal models, patients with impaired glucose tolerance, patients with type 2 diabetes mellitus, and nondiabetic hypertensive individuals, [12][13][14][15][16] we investigated the effect of RSG on AGT expression and Ang II secretion in human adipocytes.…”

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confidence: 99%

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Insulin-Mediated Upregulation of the Renin Angiotensin System in Human Subcutaneous Adipocytes Is Reduced by Rosiglitazone

et al. 2005

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Background-Obesity-associated hypertension is likely to be due to multiple mechanisms. Identification of the renin-angiotensin system (RAS) within adipose tissue does, however, suggest a potential causal role for it in obesity-associated hypertension. Obese patients are often hyperinsulinemic, but mechanisms underlying insulin upregulation of the RAS in adipose tissue are unclear. Tumor necrosis factor-␣ (TNF-␣), an inducer of angiotensinogen in hepatocytes, is elevated in hyperinsulinemic, obese individuals and may provide a link in mediating insulin upregulation of the RAS in adipose tissue. Furthermore, thiazolidinediones lower blood pressure in vivo, and downregulation of the RAS in adipose tissue may contribute to this effect. We therefore examined the effect of rosiglitazone (RSG) on the insulin-mediated upregulation of the RAS. Methods and Results-Sera were obtained from the arterial circulation and from venous blood by draining subcutaneous abdominal adipose tissue. Isolated human abdominal subcutaneous adipocytes (nϭ12) were treated with insulin (1 to 1000 nmol/L), insulin in combination with RSG (10 nmol/L), and RSG (10 nmol/L) alone to determine angiotensinogen expression and angiotensin II, bradykinin, and TNF-␣ secretion. Subcutaneous adipocytes were also treated with TNF-␣ (10 to 100 ng/mL) to examine the direct effect on angiotensinogen expression and angiotensin II secretion. The findings showed that the arteriovenous difference in angiotensin II levels was significant (Ͼ23%; PϽ0.001). Insulin increased TNF-␣ secretion in a concentration-dependent manner (PϽ0.01), whereas RSG (10 nmol/L) significantly reduced the insulin-mediated rise in TNF-␣ (PϽ0.001), as well as angiotensin and angiotensin II. TNF-␣ also increased angiotensinogen and angiotensin II in isolated adipocytes. Conclusions-The present in vivo data suggest that human subcutaneous adipose tissue is a significant source of angiotensin II. This study also demonstrates a potential TNF-␣-mediated mechanism through which insulin may stimulate the RAS and may contribute to explain obesity-associated hypertension. RSG downregulates the RAS in subcutaneous adipose tissue, and this effect may contribute to the long-term effect of RSG on blood pressure.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Insulin-Mediated Upregulation of the Renin Angiotensin System in Human Subcutaneous Adipocytes Is Reduced by Rosiglitazone

et al. 2005

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“…While rosiglitazone and metformin are typically used in the treatment of type 2 diabetes, recent studies have demonstrated that both metformin (24) and the thiazolidinediones troglitazone (49) and rosiglitazone (50) are capable of reducing the rate of conversion from impaired glucose tolerance to diabetes. Whether reduced islet amyloid formation is a basis for these effects is an interesting and important question.…”

Section: Fig 4 Amentioning

confidence: 99%

Long-Term Treatment With Rosiglitazone and Metformin Reduces the Extent of, but Does Not Prevent, Islet Amyloid Deposition in Mice Expressing the Gene for Human Islet Amyloid Polypeptide

et al. 2005

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Islet amyloid deposition in type 2 diabetes is associated with reduced ␤-cell mass. Therefore, interventions aimed at reducing islet amyloid formation may help preserve ␤-cell mass in type 2 diabetes. Rosiglitazone and metformin act by different mechanisms to improve insulin sensitivity and thereby reduce ␤-cell secretory demand, resulting in decreased release of insulin and islet amyloid polypeptide (IAPP), the unique constituent of islet amyloid deposits. We hypothesized that this reduced ␤-cell secretory demand would lead to reduced islet amyloid formation. Human IAPP (hIAPP) transgenic mice, a model of islet amyloid, were treated for 12 months with rosiglitazone (1.5 mg ⅐ kg ؊1 ⅐ day ؊1 , n ‫؍‬ 19), metformin (1 g ⅐ kg ؊1 ⅐ day ؊1 , n ‫؍‬ 18), or control (n ‫؍‬ 17). At the end of the study, islet amyloid prevalence (percent islets containing amyloid) and severity (percent islet area occupied by amyloid), islet mass, ␤-cell mass, and insulin release were determined. Islet amyloid prevalence (44 ؎ 8, 13 ؎ 4, and 11 ؎ 3% for control, metformin-, and rosiglitazone-treated mice, respectively) and severity (9.2 ؎ 3.0, 0.22 ؎ 0.11, and 0.10 ؎ 0.05% for control, metformin-, and rosiglitazonetreated mice, respectively) were markedly reduced with both rosiglitazone (P < 0.001 for both measures) and metformin treatment (P < 0.001 for both measures). Both treatments were associated with reduced insulin release assessed as the acute insulin response to intravenous glucose (2,189 ؎ 857, 621 ؎ 256, and 14 ؎ 158 pmol/l for control, metformin-, and rosiglitazonetreated mice, respectively; P < 0.05 for metformin vs. control and P < 0.005 for rosiglitazone vs. control), consistent with reduced secretory demand. Similarly, islet mass (33.4 ؎ 7.0, 16.6 ؎ 3.6, and 12.2 ؎ 2.1 mg for control, metformin-, and rosiglitazone-treated mice, respectively) was not different with metformin treatment (P ‫؍‬ 0.06 vs. control) but was significantly lower with rosiglitazone treatment (P < 0.05 vs. control). When the decreased islet mass was accounted for, the islet amyloid-related decrease in ␤-cell mass (percent ␤-cell mass/islet mass) was ameliorated in both rosiglitazoneand metformin-treated animals (57.9 ؎ 3.1, 64.7 ؎ 1.4, and 66.1 ؎ 1.6% for control, metformin-, and rosiglitazone-treated mice, respectively; P < 0.05 for metformin or rosiglitazone vs. control). In summary, rosiglitazone and metformin protect ␤-cells from the deleterious effects of islet amyloid, and this effect may contribute to the ability of these treatments to alleviate the progressive loss of ␤-cell mass and function in type 2 diabetes. Diabetes 54:2235-2244, 2005 T ype 2 diabetes is characterized by insulin resistance and islet ␤-cell secretory dysfunction. In addition, several studies (1-3) have shown that reduced ␤-cell mass is a feature of the disease. Whether this ␤-cell mass loss is progressive in nature is not clear from available data, but a recent study (3) has shown ␤-cell mass to be already reduced in individuals with impaired fasting glucose, suggesting tha...

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“…The overall risk that patients with IGT will develop diabetes is 3-9% per year in the United States (Ipp 2000). TZDs improve insulin sensitivity in a range of insulin-resistant states without diabetes, including obesity and IGT (Ghanim et al 2001;Sekino et al 2003;Bennett et al 2004).…”

Section: Use In Diabetes Preventionmentioning

confidence: 99%

Peroxisome proliferator-activated receptor-γ agonists and diabetes: Current evidence and future perspectives

Chiarelli

Marzio²

2008

VHRM

107

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Abstract:Since their initial availability in 1997, the thiazolidinediones (TZDs) have become one of the most commonly prescribed classes of medications for type 2 diabetes. In addition to glucose control, the TZDs have a number of pleiotropic effects on myriad traditional and non-traditional risk factors for diabetes. TZDs may benefi t cardiovascular parameters, such as lipids, blood pressure, infl ammatory biomarkers, endothelial function and fi brinolytic state. In this review, we summarise the experimental, preclinical and clinical data regarding the effects of the TZDs in conditions for which they are indicated and discuss their potential in the treatment of other conditions.

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Rosiglitazone improves insulin sensitivity, glucose tolerance and ambulatory blood pressure in subjects with impaired glucose tolerance

Cited by 67 publications

References 35 publications

Insulin-Mediated Upregulation of the Renin Angiotensin System in Human Subcutaneous Adipocytes Is Reduced by Rosiglitazone

Insulin-Mediated Upregulation of the Renin Angiotensin System in Human Subcutaneous Adipocytes Is Reduced by Rosiglitazone

Long-Term Treatment With Rosiglitazone and Metformin Reduces the Extent of, but Does Not Prevent, Islet Amyloid Deposition in Mice Expressing the Gene for Human Islet Amyloid Polypeptide

Peroxisome proliferator-activated receptor-γ agonists and diabetes: Current evidence and future perspectives

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Rosiglitazone improves insulin sensitivity, glucose tolerance and ambulatory blood pressure in subjects with impaired glucose tolerance

Cited by 67 publications

References 35 publications

Insulin-Mediated Upregulation of the Renin Angiotensin System in Human Subcutaneous Adipocytes Is Reduced by Rosiglitazone

Insulin-Mediated Upregulation of the Renin Angiotensin System in Human Subcutaneous Adipocytes Is Reduced by Rosiglitazone

Long-Term Treatment With Rosiglitazone and Metformin Reduces the Extent of, but Does Not Prevent, Islet Amyloid Deposition in Mice Expressing the Gene for Human Islet Amyloid Polypeptide

Peroxisome proliferator-activated receptor-&gamma; agonists and diabetes: Current evidence and future perspectives

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Product

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Peroxisome proliferator-activated receptor-γ agonists and diabetes: Current evidence and future perspectives