Diabetes, obesity, and Acrp30/adiponectin.

摘要: Diabetes mellitus (DM) is the clinical condition of inappropriate regulation blood sugar by insulin, with resulting elevation glucose and several other metabolic derangements. DM comprised two distinct entities: type 1 (DM-1), affecting minority (5%–10%), characterized destruction insulin-secreting pancreatic β cells, leading to an absence insulin. 2 (DM-2), also called adult-onset 90%–95% patients diabetes, peripheral defects in response Much work has focused on underlying pathophysiology these diseases, related a common defect—an absolute or functional loss insulin action—but differing widely pathogenesis. [For recent review, see Saltiel (25)]. Insulin, as anabolic hormone, acts promote clearance glucose, chiefly muscle through stimulation translocation GLUT4 from intracellular pools plasma membrane; liver inhibition glycogenolysis enhancement glycogen synthesis; adipose tissue uptake free fatty acids (30) its storage fat. In tissue, inhibits breakdown triglycerides resultant release inhibiting hormone-sensitive lipase. The prevalence DM-2 continued increase years, number selected areas United States increasing 3-fold over eight-year period (3), matched striking rise childhood (13). This paralleled obesity, highlighting intimate connection conditions. link been described both developed increasingly developing world, demonstrating influence lifestyle However, strong genetic links between obesity diabetes have described, supported at basic science level well. particular, derangements lipid metabolism are hallmark DM-2. morbidity associated may be directly indirectly poorly controlled lead constellation symptoms that together known syndrome, syndrome X (7,11,12). term “the deadly quartet”, coined Kaplan (11), refers abdominal resistance, dyslipidemia, hypertension found syndrome. Clearly, there many factors development progression conditions, methods counter them become major goal contemporary medicine. Recent shown while long for capacity store fat, additional important role source hormones paracrine mediators, including resistin, adipsin, leptin, TNF-α. Many groups studying physiologic molecules their Here we discuss recently identified hormone produced only adipocytes, Acrp30 (also adiponectin), central (adipocyte complement-related protein 30 kDa) serum exclusively tissue. First 1995 (28) subtractive hybridization screen identify genes induced during differentiation mouse 3T3-L1 preadipocytes up-regulated 100-fold adipocyte differentiation. Subsequently, human homolog, Apm1 (20). predicted amino acid sequence (Figure 1) contains amino-terminal signal sequence, followed nonconserved region 28 acids, 22 collagen repeats, carboxyl-terminal domain homology globular complement factor C1q. segment homologous Hib27, member family proteins animals capable hibernation, but when active state (15,28). Bacterially expressed full-length forms trimers, hexamers, higher-order structures (31); similar species seen serum, where high concentration, order 5–10 μg/mL (1,28). significance different further below. crystal structure head alone, bacteria, similarity TNF-α (29), forming homotrimer characteristic topology; terminal carboxyl termini located close proximity. Post-translational modifications include addition disialic residues (26) hydroxylation glycosylation conserved lysine molecule. Though signifi-