Metalloproteinase Changes in Diabetes

Abstract

Matrix metalloproteinases (MMPs) constitute a group of over 20 structurally-related proteins which include a Zn(++) ion binding site that is essential for their proteolytic activities. These enzymes play important role in extracellular matrix turnover in order to maintain a proper balance in its synthesis and degradation. MMPs are associated to several physiological and pathophysiological processes, including diabetes mellitus (DM). The mechanisms of DM and its complications is subject of intense research and evidence suggests that MMPs are implicated with the development and progression of diabetic microvascular complications such as nephropathy, cardiomyopathy, retinopathy and peripheral neuropathy. Recent data has associated DM to changes in the tendon structure, including abnormalities in fiber structure and organization, increased tendon thickness, volume and disorganization obtained by image and a tendency of impairing biomechanical properties. Although not fully elucidated, it is believed that DM-induced MMP dysregulation may contribute to structural and biomechanical alterations and impaired process of tendon healing.

Serum Zn/Cu Ratio Is Associated with Renal Function, Glycemic Control, and Metabolic Parameters in Japanese Patients with and without Type 2 Diabetes: A Cross-sectional Study

“…The dysregulation of matrix metalloproteinases which include a Zn ion-binding site are associated with the progression of diabetic complications via the interaction with advanced glycation end products in patients with type 2 diabetes, although the relationship between matrix metalloproteinases and serum Zn levels were not investigated in the present study (12). Furthermore, these trace elements are necessary for the activity of mitochondrial antioxidant enzymes, such as Cu/Zn superoxide dismutase (SOD), that protect the cell from reactive oxygen species toxicity (32).…”

“…Although the effect of zinc supplementation in the improvement of oxidative stress is controversial, one of the causes that the oxidative stress is present in patients with type 2 diabetes is the change in zinc metabolism (4). Moreover, a number of studies have suggested that matrix metalloproteinases which include a Zn ion-binding site are associated with the progression of diabetic microvascular complications and diabetic tendon disorders (12). Recent studies have demonstrated that the islet-restricted zinc transporter, ZnT8 ( SLC30A8 ), regulates insulin secretion (13) and hepatic insulin clearance (14), suggesting that Zn is a key biological factor in glucose homeostasis and the risk of developing type 2 diabetes (15).…”

MMP-2 salivary activity in type 2 diabetes mellitus patients

“…Moreover, clinical correlation studies suggest that high circulating MMP-2 levels may correlate with the severity of periodontitis in T2DM [24]. Nevertheless, the relationship between uncontrolled glycemia and the gelatinolytic activity of MMP-2 in the saliva of T2DM patients with periodontitis is unknown [25–27]. The main purpose of this study was to describe and compare the levels of salivary MMP-2 activity in uncontrolled glycemic T2DM patients.…”

Effect of photobiomodulation and exercise on early remodeling of the Achilles tendon in streptozotocin-induced diabetic rats

“…Moreover, the LPBM group played a role in reducing the expression of MMP-3 and MMP-13. MMP-3 works in ECM degradation after mechanical loading without cleaving fibrillar Col1 [40], facilitating directly or indirectly synthesis of ECM components, cell proliferation and differentiation [41]. On the other hand, MMP-13 is able to degrade fibrillar collagens that provide mechanical strength to tissues.…”