Diabetes

By Hunter Martinez

By Jamshed Arslan, Pharm. D., PhD.

By Jamshed Arslan Pharm.D.

Matrix metalloproteinases (MMP) are a family of endopeptidases involved in the breakdown of extracellular matrix (ECM) during both normal physiological and disease processes. MMP-2 is a zinc-dependent family member that selectively cleaves collagen and elastin, major structural components of the basement membrane. In addition, MMP-2 has been found to affect a number of non-matrix proteins such as big endothelin-1 (Fernandez-Patron et al., 1999), KISS (Takino et al., 2003), GSK3B (Kandasamy et al., 2009), and CHUK (Olivotto et al., 2013).

Adenoviruses comprise a family of medium sized, non-enveloped viruses that were originally isolated from human adenoids (Rowe et al., 1953). These viruses contain a double stranded DNA genome within an icosahedral nucleocapsid capable of penetrating an endosome without the need for envelope fusion.

Wingless-Type 5A (Wnt-5a) is a member of the WNT family of secreted signaling proteins that regulate many important developmental processes including cell proliferation, migration, differentiation, fate determination and embryonic patterning. WNT signal proteins affect the cell via three known WNT signal transduction pathways. The canonical WNT signaling pathway regulates gene transcription, the non-canonical planar cell polarity pathway regulates cytoskeletal formation, and the non-canonical Wnt/calcium pathway regulates cellular calcium levels.

Peroxisome proliferators are non-genotoxic carcinogens which are purported to exert their effect on cells by interacting with members of the nuclear hormone receptor superfamily known as peroxisome proliferator activated receptors (PPARs). There are four of these nuclear hormone receptors known to date, and they are ligand-dependent intracellular proteins that stimulate downstream gene transcription of genes such as acyl coenzyme A oxidase and cytochrome P450 (CYP450). Activation occurs through direct binding to specific DNA response elements following activation by an appropriate ligand.

GLUT4 is an insulin-sensitive glucose transporter that facilitates insulin-stimulated glucose uptake in adipose tissue, skeletal muscle, and cardiac tissues that specifically express this protein. It is a twelve transmembrane domain multi-pass protein found only in the endosome system and perinuclear cytoplasm. Upon insulin stimulation, GLUT4 translocates to the cell surface. Because of its role in glucose homeostasis, GLUT4 is the key regulator of obesity and obesity-related disease.

SREBP1 (sterol-regulatory-element-binding protein 2) is a basic-helix-loop-helix-leucine zipper (bHLH-ZIP) transcription factor. It regulates sterol and cholesterol homeostasis by controlling enzymes involved in cholesterol synthesis and uptake, e.g. HMG-CoA. The SREBP1 antibody was used in fundamental studies to dissect SREBP1 domains and downstream signaling (1).