Skeletal myoblast transplantation for attenuation of hyperglycaemia, hyperinsulinaemia and glucose intolerance in a mouse model of type 2 diabetes mellitus.

AIMS/HYPOTHESIS: We aimed to demonstrate the feasibility and efficacy of intra-muscular transplantation of human skeletal myoblasts (hSkMs) for attenuation of hyperglycaemia and improvement of insulin sensitivity using a mouse model of type 2 diabetes mellitus. METHODS: KK Cg-Ay/J mice, aged 12 to 14 weeks, underwent an initial intraperitoneal glucose tolerance test (GTT) and were divided into the following groups: KK control group, basal medium (M199) only; KK myoblast group, with hSkM transplantation; KK fibroblast group, with human fibroblast transplantation. Non-diabetic C57BL mice were used as an additional normal control and also had hSkM transplantation. Cells were transplanted intra-muscularly into the skeletal muscles of the mice. All animals were treated with ciclosporin for 6 weeks only. HbA(1c) and fasting GTT, as well as serum adiponectin, cholesterol, insulin and triacylglycerol were studied. RESULTS: Immunohistochemistry studies showed extensive survival of the transplanted hSkMs in the skeletal muscles at 12 weeks, with nuclei of the hSkMs integrated into the host muscle fibres. Repeat GTT showed a significant decrease in glucose concentrations in the KK myoblast group compared with the KK control and KK fibroblast groups. The KK myoblast group also had reduced mean HbA(1c), cholesterol, insulin and triacylglycerol, and increased adiponectin compared with the KK control and KK fibroblast groups. C57BL mice showed no change in glucose homeostasis after hSkM transplant. CONCLUSIONS/INTERPRETATION: Human skeletal myoblast transplantation attenuated hyperglycaemia and hyperinsulinaemia and improved glucose tolerance in the KK mouse. This novel approach of improving muscle insulin resistance may be a potential alternative treatment for type 2 diabetes mellitus.

Diagnostic transgastric flexible peritoneoscopy: is pure natural orifice transluminal endoscopic surgery a fantasy?

We present the first transgastric peritoneoscopy in a 20-year-old man. The objectives were to evaluate the impact of the site of viscerotomy on the technical feasibility of natural orifice transluminal endoscopic surgery (NOTES), assess transgastric peritoneoscopy as a complementary procedure, determine the safety and efficacy of NOTES, and attempt inspection/biopsy of the gallbladder. The patient was admitted with a benign gastric outlet obstruction, chronic cholecystitis and radiological suspicion of a mass in the gallbladder which was not visualised on diagnostic laparoscopy. Complementary transgastric peritoneoscopy was performed to gain deeper penetration of the tumour with the flexible tip of the gastroscope. The visceral "aperture" was created in the antrum where gastrojejunal anastomosis would be fashioned. Laparoscopic transillumination of the anterior gastric wall facilitated this part of the procedure. During transgastric peritoneoscopy, the gallbladder and structures in the upper and left hemi-abdomen appeared retrograde due to the unusual location of the gastrotomy. The right hemi-abdomen and pelvis were easily examined with a "straight shaft" approach. The gallbladder could not be identified with exploratory laparoscopy and transgastric peritoneoscopy. Due to risk of visceral injury, open gastrojejunal anastomosis and cholecystectomy were performed. Intraoperatively, an inflamed, thick-walled gallbladder was found adherent to the proximal duodenum. Transgastric peritoneoscopy was safely performed in our patient. The postoperative course was uneventful. Our patient showed significant improvement at 13 weeks after surgery without any procedure-related complication. In conclusion, transgastric peritoneoscopy may be used to complement diagnostic laparoscopy. Laparoscopic assistance during transluminal access facilitates simple tasks inside the peritoneal cavity to be performed safely.