No abstract

Hyperinsulinemia, loss of glucose-stimulated insulin secretion (GSIS), and peripheral insulin resistance coexist in non-insulin-dependent diabetes mellitus (NIDDM).Because free fatty acids (FFA) can induce these same abnormalities, we studied their role in the pathogenesis of the NIDDM of obese Zucker diabetic fatty (ZDF-drt) rats from 5 weeks of age (before the onset ofhyperglycemia) until 14 weeks. Two weeks prior to hyperglycemia, plasma FFA began to rise progressively, averaging 1.9 ± 0.06 mM at the onset of hyperglycemia (P < 0.001 vs. controls). At this time GSIS was absent and fl-cell GLUT-2 glucose transporter was decreased. The triacylglycerol content of prediabetic islets rose to 10 times that of controls and was correlated with plasma FFA (r = 0.825; P < 0.001), which, in turn, was correlated with the plasma glucose concentration (r = 0.873; P < 0.001). Reduction of hyperlipacidemia to 1.3 ± 0.07 mM by pair feeding with lean littermates reduced all (I-cell abnormalities and prevented hyperglycemia. Normal rat islets that had been cultured for 7 days in medium containing 2 mM FFA exhibited increased basal insulin secretion at 3 mM glucose, and first-phase GSIS was reduced by 68%; in prediabetic islets, first-phase GSIS was reduced by 69% by FFA. The results suggest a role for hyperlipacidemia in the pathogenesis of NIDDM; resistance to insulin-mediated antilipolysis is invoked to explain the high FFA despite hyperinsulinemia, and sensitivity of (3 cells to hyperlipacedemia is invoked to explain the FFA-induced loss of GSIS.Despite decades of intensive research the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM), a disorder that affects 2-5% of the world's population, remains obscure. Because it may precede the onset of hyperglycemia by many years, insulin resistance is widely viewed as the primary abnormality in the disease (1). In this formulation the associated hyperinsulinemia is viewed as a secondary compensation by 13 cells for the antecedent insulin insensitivity; when hyperglycemia begins, it is regarded as reflecting an inability of hypersecreting 13 cells to meet an ever-increasing insulin requirement (2). However, neither the mechanism by which 13 cells initially maintain a high enough level of insulin secretion to prevent hyperglycemia despite increasing insulin resistance nor the cause of their ultimate failure to do so has been identified. 13-Cell failure is accompanied in human and rodent NIDDM by complete loss of glucose-stimulated insulin secretion (GSIS) (3,4) and, in all rodent models thus far studied, by a parallel reduction in ,8 cells displaying GLUT-2, the high-Km facilitative glucose transporter (4-7).Long-chain fatty acids, which may be central to the development of insulin resistance in NIDDM (8, 9), can stimulate basal insulin secretion (10-13) and inhibit GSIS in isolated islets (13)(14)(15)(16)(17). This suggests a scheme that could account for the 13-cell abnormalities in pre-NIDDM and NIDDM and explain the relationship between insulin resistance and...

No abstract

We developed a methodology using 3D bio-printing technology to create a functional in vitro vascular channel with perfused open lumen using only cells and biological matrices. The fabricated vasculature has a tight, confluent endothelium lining, presenting barrier function for both plasma protein and high-molecular weight dextran molecule. The fluidic vascular channel is capable of supporting the viability of tissue up to 5mm in distance at 5 million cells/mL density under the physiological flow condition. In static-cultured vascular channels, active angiogenic sprouting from the vessel surface was observed whereas physiological flow strongly suppressed this process. Gene expression analysis were reported in this study to show the potential of this vessel model in vascular biology research. The methods have great potential in vascularized tissue fabrication using 3D bio-printing technology as the vascular channel is simultaneously created while cells and matrix are printed around the channel in desired 3D patterns. It can also serve as a unique experimental tool for investigating fundamental mechanisms of vascular remodeling with extracellular matrix and maturation process under 3D flow condition.

Although few studies tested the effects of activated PRP on hair growth, this research provides support for possible clinical application of autologous PRP and its secretory factors for promotion of hair growth.