Septate junctions regulate gut homeostasis through regulation of stem cell proliferation and enterocyte behavior in Drosophila

Smooth septate junctions (sSJs) contribute to the epithelial barrier, which restricts leakage of solutes through the paracellular route of epithelial cells in the Drosophila midgut. We previously identified three sSJ-associated membrane proteins, Ssk, Mesh, and Tsp2A, and showed that these proteins were required for sSJ formation and intestinal barrier function in the larval midgut. Here, we investigated the roles of sSJs in the Drosophila adult midgut. Depletion of any of the sSJ-proteins from enterocytes resulted in remarkably shortened lifespan and intestinal barrier dysfunction in flies. Interestingly, the sSJ protein-deficient flies showed intestinal hypertrophy accompanied by accumulation of morphologically abnormal enterocytes. The phenotype was associated with increased stem cell proliferation and activation of the MAP kinase and Jak-Stat pathways in stem cells. Loss of cytokines Unpaired2 and Unpaired3, which are involved in Jak-Stat pathway activation, suppressed the intestinal hypertrophy, but not the increased stem cell proliferation, in flies lacking Mesh. The present findings suggest that SJs play a crucial role in maintaining tissue homeostasis through regulation of stem cell proliferation and enterocyte behavior in the Drosophila adult midgut.Summary statementDepletion of smooth septate junction-associated proteins from enterocytes in the Drosophila adult midgut results in intestinal hypertrophy accompanied by accumulation of morphologically aberrant enterocytes and increased stem cell proliferation.

Adaptation of small intestinal membrane transport processes during diabetes mellitus in rats

Intestinal amino acid and glucose transport is increased in various disease states and physiological circumstances. This enhancement is generally due to an increase in transport capacity (Vmax) without a change in carrier affinity (KD). Furthermore, the increase in transport capacity is too large to be attributed, in most cases, to simple intestinal hypertrophy. In the streptozotocin-treated chronically diabetic rat model, specific binding indicated an enhanced total number of glucose carriers in the small intestine compared with controls. Furthermore, autoradiography reveals that specific phlorizin (i.e., glucose) binding extends into the intervillous region of the intestine, while in age-matched controls binding is confined to the villous tip. These studies suggest that during experimental diabetes mellitus in rats, enhanced intestinal nutrient absorption may occur as a consequence of recruitment of carriers into previously nontransporting enterocytes. This review looks at ways in which this alteration may be influenced, and examines the expression of various isoforms of Na–K ATPase during streptozocin-induced diabetes mellitus.Key words: intestinal transport, glucose, sodium–potassium ATPase, adaptation.

Body condition of willow ptarmigan parasitized by cestodes during winter

Sixty-two adult male willow ptarmigan (Lagopus lagopus) were collected over 3 days in April 1979 from a single flock along the Hudson Bay coast of Ontario. Twenty-one ptarmigan contained cestodes (genus Raillietina) in the anterior of the small intestine and 41 were free of cestodes. Each ptarmigan was dissected into its principal voluntary muscles, liver, and intestinal components, and the entire body was subjected to neutral fat extraction. Parasitized willow ptarmigan had significantly heavier empty small intestinal weights than nonparasitized birds. All other variables pertaining to the fat–protein reserve status were very similar between the two groups. The larger small intestines of parasitized ptarmigan were shown, statistically, to be attributable to the presence of cestodes and not to effects of varying body size. There were significant correlations between the weight of the small intestine and the weight of cestodes (r = 0.677) and the volume of cestodes (r = 0.667) but not the number of cestodes (r = 0.414) in any given ptarmigan. The hypertrophic response was confined to the small intestine and was small (approximately 1.2 g of wet tissue) compared with the amount of intestinal hypertrophy that normally occurs with change of season and diet. This population of willow ptarmigan readily accommodates to cestodes with no detectable impairment of its winter nutrient and energy balance.

Effect of glucose or fructose feeding on cholesterol synthesis in diabetic animals

Previous studies have demonstrated that cholesterol synthesis is increased twofold in the small intestines of rats with streptozotocin-induced diabetes. The purpose of the present study was to determine the effect of adding glucose or fructose to standard rat chow on cholesterol synthesis in control and diabetic rats. In control rats a 25% glucose or fructose diet fed for 21 days markedly inhibited hepatic cholesterol synthesis in the liver. In contrast, in diabetic animals only fructose inhibited hepatic cholesterol synthesis. In both control and diabetic animals the addition of these simple sugars to the diet did not markedly alter extrahepatic cholesterol synthesis. The enhancement of small intestinal cholesterol synthesis observed in diabetic animals was present regardless of the dietary manipulations. Further studies demonstrated that the addition of smaller concentrations of fructose (10%) to standard rat chow decreased hepatic cholesterol synthesis in both control and diabetic rats. Similarly the addition of fructose to the diet of control and diabetics for a period as short as 2 days was also sufficient to inhibit hepatic cholesterol synthesis. In both control and diabetic animals, fructose feeding decreased hepatic 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity but did not alter the percentage of HMG-CoA reductase in the active form. Finally, the intestinal hypertrophy and stimulation of intestinal cholesterogenesis that are characteristic of streptozotocin-induced diabetes occurred when either glucose or fructose was the sole caloric source.