Insulin restores neuronal nitric oxide synthase expression and function that is lost in diabetic gastropathy
J. Clin. Invest. Crystal C. Watkins, et al. 106:373 doi:10.1172/JCI8273 [Go to this article.]

Figure 2
Diabetic mice have delayed gastric emptying that is not due to hyperglycemia and enlarged stomachs. (a) Gastric emptying (20% dextrose) in diabetic mice. NOD-prediabetic mice (filled circles), age 10 weeks, have gastric emptying rates similar to wild-type mice (filled squares). STZ-diabetic mice (open triangles) and NOD-diabetic mice (open circles) exhibit significantly delayed gastric emptying, similar to that of nNOS^–/– mice (filled triangles). Each data point represents the mean (± SEM) from groups of four to six animals. All diabetic animals exhibit some delay in gastric emptying, and this is reflected in the error bars (SEM) as shown. In some instances, the error bars are small and contained within the symbols. This experiment has been repeated twice with the same results. (b) Serum glucose levels of STZ-diabetic mice after insulin treatment. STZ-diabetic mice were either sham operated (n = 5) or treated with subcutaneous placement of an insulin-releasing implant (n = 5; see Methods). Then, serum glucose levels were determined at the indicated time points. The data shown are the means (± SEM) of five measurements for each time point. Serum glucose levels decline to around 100 mg/dL by 12 hours and remain at similar levels for 48 hours. (c) Gastric emptying in STZ-diabetic mice after 12 hours of insulin treatment. STZ-diabetic mice were either sham operated (STZ_d(s)) or treated with subcutaneous placement of an insulin-releasing implant (STZ_d(ii)) 12 hours before determination of gastric emptying. The data shown are the means (± SEM) for five to seven measurements per time point. (d) Stomachs excised from wild-type, NOD-prediabetic (NOD_pd), nNOS^–/–, NOD-diabetic (NOD_d), and STZ-diabetic (STZ_d) mice were photographed to demonstrate the enlargement of the stomach in NOD-diabetic mice. The pictures are representative of five to eight specimens examined for each group of animals. (e) Stomachs from wild-type, NOD-prediabetic, nNOS^–/–, NOD-diabetic, and STZ-diabetic mice were weighed after fasting for 4 hours. Data shown are the means (± SEM) for five specimens in each group. The stomachs from the NOD-diabetic and nNOS^–/– mice weighed significantly more than those from wild-type mice. ^AP < 0.05 for nNOS^–/– stomachs compared with wild-type and for NOD-diabetic specimens compared with NOD-prediabetic.