Previous study have demonstrated that Tangshen Formula (TSF) could attenuate colonic histomorphological remodeling in the diabetic rat model induced by high fat diet plus low dosage streptozotocin (STZ). However, it is not clear whether TSF has same effect on small intestine and the effect on biomechanical properties of bowel. The aim of this study is to investigate the effect of TSF on histomorphological and biomechanical remodeling of small intestine and colon by using Zucker Diabetic Fatty (ZDF) Rat model.

ZDF rats (obese fa/fa) with blood glucose higher than 11.7 mmol/L were divided into ZDF group (diabetic control group) and ZDF + TSF group (TSF treatment group), the later were intragastrically administered TSF. The ZDF rats (lean fa/+) were served as normal control (ZL) group. The rats in the ZL and ZDF groups were administered with saline. The experimental period covered from 8 weeks to 24 weeks. At the end of experiment, the ileal and colonic segments were studied in vitro. The histomorphometry and biomechanical parameters were measured.

Compared with ZL group histomorphologically, the wet weight per unit length, wall thickness, wall area and fractions of total and type I and type III collagen in different layers for both ileum and colon increased in ZDF group. Those increasing parameters were partially inhibited in ZDF + TSF group. Compared with ZL group biomechanically, ZDF and ZDF + TSF groups had smaller opening angle and residual strain in ileum, and bigger opening angle and residual strain in colon. Whereas the wall became softer in circumferential direction and stiffer in longitudinal direction for both ileum and colon. However, no difference of biomechanical parameters was found between ZDF and ZDF + TSF groups.

The histomorphological and biomechanical remodeling of ileum and colon were happened in ZDF rats （obese fa/fa）. TSF could partly attenuate ileal and colonic histomorphological remodeling rather than biomechanical remodeling.

Constipation is a major complications of diabetes mellitus. With the accelerating prevalence of diabetes worldwide and an aging population, there is considerable research interest regarding the altered function and structure of the gastrointestinal tract in diabetic patients. Despite current advances in hyperglycemic treatment strategies, the specific pathogenesis of diabetic constipation remains unknown. Patients with constipation, may be reluctant to eat regularly, which may worsen glycemic control and thus worsen symptoms associated with underlying diabetic bowel disease. This paper presents a review of the complex relationship between diabetes and constipation, exploring the morphological alterations and biomechanical remodeling associated with intestinal motility dysfunction, as well as alterations in intestinal neurons, cellular signaling pathways, and oxidative stress. Further studies focusing on new targets that may play a role in the pathogenesis of diabetic constipation may, provide new ideas for the development of novel therapies to treat or even prevent diabetic constipation.

Subcutaneous and inhaled insulins are associated with needle phobia, lipohypertrophy, lipodystrophy, and cough in diabetes treatment. Oral nanoinsulin has been developed, reaping the physiologic benefits of peroral administration. This review profiles intestinal receptors exploitable in targeted delivery of oral nanoinsulin. Intestinal receptor targeting improves oral insulin bioavailability and sustains blood glucose-lowering response. Nonetheless, these studies are conducted in small animal models with no optimization of insulin dose, targeting ligand type and content, and physicochemical and molecular biologic characteristics of nanoparticles against the in vivo/clinical diabetes responses as a function of the intestinal receptor population characteristics with diabetes progression. The interactive effects between nanoinsulin and antidiabetic drugs on intestinal receptors, including their up-/downregulation, are uncertain. Sweet taste receptors upregulate SGLT-1, and both have an undefined role as new intestinal targets of nanoinsulin. Receptor targeting of oral nanoinsulin represents a viable approach that is relatively green, requiring an in-depth development of the relationship between receptors and their pathophysiological profiles with physicochemical attributes of the oral nanoinsulin. SIGNIFICANCE STATEMENT: Intestinal receptor targeting of oral nanoinsulin improves its bioavailability with sustained blood glucose-lowering response. Exploring new intestinal receptor and tailoring the design of oral nanoinsulin to the pathophysiological state of diabetic patients is imperative to raise the insulin performance to a comparable level as the injection products.