Serum transforming growth factor-beta 1 levels in normoalbuminuric and normotensive patients with type 2 diabetes. Effect of metformin and rosiglitazone

Abstract

OBJECTIVE: a)To determine serum Transforming Growth Factor-beta 1 (TGF-β1) levels in patients with type 2 diabetes who do not have diabetes related complications and in healthy controls, b) to evaluate the effects of metformin and rosiglitazone on TGF-β1 levels. DESIGN: In the washout period, 61 patients with Fasting Plasma Glucose levels (FPG) higher than 140 mg/dl, Postprandial Glucose (PPG) levels higher than 180 mg/dl and A1c levels exceeding 6.5% were treated with glimperide. After 4 weeks, 39 of these patients were randomised to receive either metformin or rosiglitazone for 12 weeks. Thirty healthy controls were also studied. RE-SULTS: There were no significant differences with regard to age, gender, body weight and BMI between patients and healthy controls. Type 2 diabetics had higher waist circumference, FPG, total cholesterol, LDL-cholesterol and triglyceride levels. Baseline TGF-β1 levels in diabetics were higher than in controls (29.84±7.04 ng/ml vs 11.37±4.06 ng/ml, p<0.001). Metformin or rosiglitazone did not significantly modify the TGF-β1 levels. In a multiple regression analysis FPG was the only variable that was significantly associated with plasma TGF-β1 levels. CON-CLUSION: The elevated levels of TGF-β1 in subjects with type 2 diabetes possibly indicate a tendency for renal and endothelial damage in such patients. The association of TGF-β1 with FPG possibly links poor diabetic control to vascular damage, leading to diabetic complications. Lack of changes in the levels of TGF-β1 after therapy may reflect inadequate therapy duration.

Association of TGF-β1 Polymorphism with Type 2 Diabetes Mellitus and Diabetic Nephropathy in Saudi Patients

“…Moreover, in vitro studies found that TGF-β1 is responsible for development of mouse β-cells, and this may be explain the increase of TGF-β1 in T2DM which result from increase insulin demand. Previously, several studies showed high TGF-β1 levels in T2DM (Yener et al, 2008). Present study is similar to previous studies which shows higher TGF-β1 level in T2DM.…”

Protection from β-cell apoptosis by inhibition of TGF-β/Smad3 signaling

“…While we infer that FFA signals promote autocrine TGF-β1 secretion from β-cells within the islets thus activating Smad3 signaling, we cannot exclude the possibility that other cells within the islets or within the pancreatic milieu serve as a paracrine source for TGF-β's actions. Indeed, circulating levels of TGF-β1 are increased in human T2D patients 58,59 and in HFD-fed mice 60 , thus allowing for the possibility of paracrine modes of activation of Smad3 signaling.…”

Prolactin anterior pituitary expression and circulating levels are reduced in obese and diabetic rats: role of TGF-β and TNF-α

“…TGF-␤ and TNF-␣ increase in the circulation of obese and diabetic humans (15,19,29,61,63), HFD-fed rodents (20,61), and STZ-diabetic rats (4,21,22). TGF-␤ promotes adiposity and glomerular pathology in obesity and diabetes, and both the adipose and renal tissues are major sources of TGF-␤ released into the circulation (14,22,23,61).…”

“…In the present work, we investigated whether the production of PRL is downregulated in the AP of obese and diabetic rats and evaluated whether alterations in the AP expression of TGF-␤ and/or TNF-␣ correlated with these changes. TGF-␤ and TNF-␣ increase in the circulation of obese and diabetic patients (15,19,29,61,63) and play important roles in insulin resistance and diabetes pathophysiology (59,61). Also, these cytokines and their receptors are ubiquitously expressed in a variety of tissues from rodents and humans, including the AP PRL-producing cell (lactotrope) (17,65), where TGF-␤ inhibits (24,49) and TNF-␣ can stimulate (27,36), but also inhibit (30,58), PRL synthesis and release; however, there is little or no information regarding the actions of TNF-␣ or TGF-␤ on PRL secretion in the context of metabolic diseases.…”