Type 1 diabetes is an autoimmune disease caused by permanent destruction of insulin-producing pancreatic beta cells and requires lifelong exogenous insulin therapy. Recently, islet transplantation has been developed, and although there have been significant advances, this approach is not widely used clinically due to the poor survival rate of the engrafted islets. We hypothesized that improving survival of engrafted islets through ex vivo genetic engineering could be a novel strategy for successful islet transplantation. We transduced islets with adenoviruses expressing betacellulin, an epidermal growth factor receptor ligand, which promotes beta-cell growth and differentiation, and transplanted these islets under the renal capsule of streptozotocin-induced diabetic mice. Transplantation with betacellulin-transduced islets resulted in prolonged normoglycemia and improved glucose tolerance compared with those of control virus-transduced islets. In addition, increased microvascular density was evident in the implanted islets, concomitant with increased endothelial von Willebrand factor immunoreactivity. Finally, cultured islets transduced with betacellulin displayed increased proliferation, reduced apoptosis and enhanced glucose-stimulated insulin secretion in the presence of cytokines. These experiments suggest that transplantation with betacellulin-transduced islets extends islet survival and preserves functional islet mass, leading to a therapeutic benefit in type 1 diabetes.
Animals ; Apoptosis ; Betacellulin ; Cell Proliferation ; Diabetes Mellitus, Experimental/*surgery ; Glucose Intolerance/*surgery ; Humans ; Insulin-Secreting Cells/*metabolism/physiology ; Intercellular Signaling Peptides and Proteins/genetics/*metabolism ; *Islets of Langerhans Transplantation ; Mice ; Mice, Inbred C57BL ; Rats

Being overweight itself is associated with increased mortality and morbidities from serious diseases. Previous papers have demonstrated a solid line of evidence that nonoperative methods alone have not been effective in achieving a medically significant stable weight loss in severely obese patients. It has been shown that the majority of patients regain all the weight lost over the next five years. Surgical treatment is medically necessary because it is the only proven method of achieving longterm weight control for the morbidly obese individuals. Surgical treatment is not a cosmetic procedure. Morbid obesity correlates with a Body Mass Index (BMI) of 40 kg/m2 or 35 kg/m2 with comobidities such as hypertension, hypertrophic cardiomyopathy, sleep apnea, hypoventilation, glucose intolerance, and diabetes mellitus in western countries. However, in Asian countries including Korea, the indications for surgical treatment of obesity should be reestablished. Surgical methods include gastric restrictive, malabsorptive, and combined. Recently, laparoscopic surgery has been introduced in the field of bariatric surgery.
Asian Continental Ancestry Group ; Bariatric Surgery* ; Body Mass Index ; Cardiomyopathy, Hypertrophic ; Diabetes Mellitus ; Glucose Intolerance ; Humans ; Hypertension ; Hypoventilation ; Korea ; Laparoscopy ; Mortality ; Obesity ; Obesity, Morbid ; Overweight ; Sleep Apnea Syndromes ; Weight Loss