Kendig DM, Ets HK, Moreland RS. Effect of type II diabetes on male rat bladder contractility. Am J Physiol Renal Physiol 310: F909 -F922, 2016. First published January 28, 2016 doi:10.1152/ajprenal.00511.2015.-Type II diabetes is the most prevalent form of diabetes. One of the primary complications of diabetes that significantly affects quality of life is bladder dysfunction. Many studies on diabetic bladder dysfunction have been performed in models of type I diabetes; however, few have been performed in animal models of type II diabetes. Using the Zucker Diabetic Fatty (ZDF) rat model of type II diabetes, we examined the contractility and sensitivity of bladder smooth muscle in response to mediators of depolarization-induced contraction, muscarinic receptor-mediated contraction, ATP-induced contraction, and neurogenic contraction. Studies were performed at 16 and 27 wk of age to monitor the progression of diabetic bladder dysfunction. Voiding behavior was also quantified. The entire bladder walls of diabetic rats were hypertrophied compared with that of control rats. Contractility and sensitivity to carbachol and ATP were increased at 27 wk in bladder smooth muscle strips from diabetic rats, suggesting a compensated state of diabetic bladder dysfunction. Purinergic signaling was increased in response to exogenous ATP in bladders from diabetic animals; however, the purinergic component of neurogenic contractions was decreased. The purinergic component of neurogenic contraction was reduced by P2X receptor desensitization, but was unchanged by P2X receptor inhibition in diabetic rats. Residual and tetrodotoxin-resistant components of neurogenic contraction were increased in bladder strips from diabetic animals. Overall, our results suggest that in the male ZDF rat model, the bladder reaches the compensated stage of function by 27 wk and has increased responsiveness to ATP. diabetic bladder dysfunction; Zucker diabetic fatty rat; muscarinic receptors; purinergic receptors; electrical field stimulation DIABETES MELLITUS (DM) IS a disorder of carbohydrate metabolism typically characterized by defective insulin secretion or insulin resistance and subsequent hyperglycemia. In the past few decades, the prevalence of DM has been on the rise (1, 33), and lower urinary tract symptoms (LUTS) are among the most common complications of diabetes affecting up to 80% of patients (14). The most common and bothersome LUTS in diabetes is bladder dysfunction, with over 50% of diabetic patients experiencing some form of bladder dysfunction (48). The primary classic symptom diabetic patients exhibit is increased residual urine volume after voiding (23). More recent research suggests a combination of both storage and voiding problems (14). Experimental evidence now suggests a temporal profile of the development of diabetic bladder dysfunction (15). There is a progression from the compensated state, during which the bladder undergoes hypertrophy and the muscle becomes hypercontractile, to the decompensated state, when the muscle is hyp...

Our results suggested that changes in fecal microbiota composition of children with clinical diarrhea are associated with certain demographic factors that should be considered before designing a prophylactic intervention. Delivery of certain Lactobacillus species and Bifidobacterium species or a diet rich in bifidogenic components that promote growth of Bifidobacterium species could provide a prophylactic effect to ameliorate the effect of diarrhea in children at risk.

Trappanese DM, Sivilich S, Ets HK, Kako F, Autieri MV, Moreland RS. Regulation of mitogen-activated protein kinase by protein kinase C and mitogen-activated protein kinase phosphatase-1 in vascular smooth muscle. Am J Physiol Cell Physiol 310: C921-C930, 2016. First published April 6, 2016; doi:10.1152/ajpcell.00311.2015.-Vascular smooth muscle contraction is primarily regulated by phosphorylation of myosin light chain. There are also modulatory pathways that control the final level of force development. We tested the hypothesis that protein kinase C (PKC) and mitogen-activated protein (MAP) kinase modulate vascular smooth muscle activity via effects on MAP kinase phosphatase-1 (MKP-1). Swine carotid arteries were mounted for isometric force recording and subjected to histamine stimulation in the presence and absence of inhibitors of PKC [bisindolylmaleimide-1 (Bis)], MAP kinase kinase (MEK) (U0126), and MKP-1 (sanguinarine) and flash frozen for measurement of MAP kinase, PKC-potentiated myosin phosphatase inhibitor 17 (CPI-17), and caldesmon phosphorylation levels. CPI-17 was phosphorylated in response to histamine and was inhibited in the presence of Bis. Caldesmon phosphorylation levels increased in response to histamine stimulation and were decreased in response to MEK inhibition but were not affected by the addition of Bis. Inhibition of PKC significantly increased p42 MAP kinase, but not p44 MAP kinase. Inhibition of MEK with U0126 inhibited both p42 and p44 MAP kinase activity. Inhibition of MKP-1 with sanguinarine blocked the Bis-dependent increase of MAP kinase activity. Sanguinarine alone increased MAP kinase activity due to its effects on MKP-1. Sanguinarine increased MKP-1 phosphorylation, which was inhibited by inhibition of MAP kinase. This suggests that MAP kinase has a negative feedback role in inhibiting MKP-1 activity. Therefore, PKC catalyzes MKP-1 phosphorylation, which is reversed by MAP kinase. Thus the fine tuning of vascular contraction is due to the concerted effort of PKC, MAP kinase, and MKP-1.bisindolylmaleimide-1; U0126; sanguinarine; caldesmon; CPI-17; phos-tag gel electrophoresis EXTRACELLULAR SIGNAL-REGULATED kinase 1/2 mitogen-activated protein kinase (MAP kinase; also known as p42/p44 MAP kinase) is a serine/threonine protein kinase that has been identified in several types of smooth muscle (7,10,19). MAP kinase is activated via dual phosphorylation of Thr 187 and Tyr 185 catalyzed by MAP kinase kinase (MEK) and has been shown to play a significant role in activating several proteins required for cell growth in proliferating dedifferentiated smooth muscle cells (24,26). However, the role of MAP kinase in differentiated, contractile smooth muscle cells is not as well understood.In differentiated smooth muscle, it has been suggested that MAP kinase may be involved in calcium-independent regulation of smooth muscle contraction (17). MAP kinase has been shown to phosphorylate the thin filament protein caldesmon and relieve its inhibitory action on the actin-activated myosin ATPase, ...

No abstract