MYH9 nephropathy.

MYH9-related disorder is an autosomal dominant disease caused by a mutation in the MYH9 gene, which encodes nonmuscle myosin heavy chain IIA (NMMHC-IIA). This disease is characterized by giant platelets, thrombocytopenia, granulocyte inclusion bodies, proteinuria, and high-pitch sensorineural deafness. Nephropathy has been observed in 30% of patients with MYH9-related disorder. The characteristic features are early onset proteinuria and rapidly progressing renal disorder. However, the prognosis of MYH9 nephropathy remains unclear. Herein, we describe a 36-year-old woman who presented with proteinuria and was diagnosed with MYH9 nephropathy via renal biopsy and gene analysis. Her proteinuria improved after administration of an angiotensin II receptor blocker, but was aggravated after changing to a calcium channel blocker.

Association between blood pressure and target organ damage in patients with chronic kidney disease and hypertension: results of the APrODiTe study.

Blood pressure control is the most established practice for preventing the progression of chronic kidney disease. Evidence addressing blood pressure control status or nocturnal blood pressure dipping in Korean hypertensive patients with chronic kidney disease is scarce. We recruited 1317 hypertensive patients (chronic kidney disease stages 2-4, median age 58) from 21 centers in Korea. These patients underwent office and ambulatory blood pressure monitoring. High office and ambulatory blood pressure were defined as >140/90 mm Hg and >135/85 mm Hg (daytime)/ >120/70 mm Hg (nighttime), respectively. The blood pressure control status was as follows: true controlled (19%), white-coat (4.3%), masked (33.9%) and sustained uncontrolled (42.3%) hypertension. The dipping status was as follows: extreme-dipping (14.9%), dipping (33.3%), non-dipping (34.5%) and reverse-dipping (17.3%). Masked and sustained hypertension as well as non-dipping/reverse-dipping was more apparent in proportion to renal dysfunction and the extent of proteinuria. Ageing (58 years), male gender, obesity, diabetic nephropathy and proteinuria (>300 mg g(-1) Cr or dipstick proteinuria1+) were independently associated with sustained uncontrolled hypertension. Diabetic nephropathy, old age, a history of stable angina/heart failure, advanced renal dysfunction and higher proteinuria levels were also significantly associated with non-dipping and reverse-dipping. Half of Korean chronic kidney disease patients had uncontrolled blood pressure and a non-dipping nocturnal blood pressure pattern. Future studies are warranted to assess the predictive values of ambulatory blood pressure for cardiorenal events in Korean chronic kidney disease patients.

Cephalic phase insulin secretion is KATP channel independent.

Glucose-induced insulin secretion from pancreatic ß-cells critically depends on the activity of ATP-sensitive K⁺ channels (KATP channel). We previously generated mice lacking Kir6.2, the pore subunit of the ß-cell KATP channel (Kir6.2(-/-)), that show almost no insulin secretion in response to glucose in vitro. In this study, we compared insulin secretion by voluntary feeding (self-motivated, oral nutrient ingestion) and by forced feeding (intra-gastric nutrient injection via gavage) in wild-type (Kir6.2(+/+) and Kir6.2(-/-) mice. Under ad libitum feeding or during voluntary feeding of standard chow, blood glucose levels and plasma insulin levels were similar in Kir6.2(+/+) and Kir6.2(-/-) mice. By voluntary feeding of carbohydrate alone, insulin secretion was induced significantly in Kir6.2(-/-) mice but was markedly attenuated compared with that in Kir6.2(+/+) mice. On forced feeding of standard chow or carbohydrate alone, the insulin secretory response was markedly impaired or completely absent in Kir6.2(-/-) mice. Pretreatment with a muscarine receptor antagonist, atropine methyl nitrate, which does not cross the blood-brain barrier, almost completely blocked insulin secretion induced by voluntary feeding of standard chow or carbohydrate in Kir6.2(-/-) mice. Substantial glucose-induced insulin secretion was induced in the pancreas perfusion study of Kir6.2(-/-) mice only in the presence of carbamylcholine. These results suggest that a KATP channel-independent mechanism mediated by the vagal nerve plays a critical role in insulin secretion in response to nutrients in vivo.

Immunohistochemical analysis of cholecystokinin A receptor distribution in the rat pancreas.

Cholecystokinin (CCK) plays a major role in the regulation of pancreatic enzyme secretion based on its binding to the CCK-A receptor (CCK-AR). While CCK-AR is known to be expressed in rat islet B cells, the localization of CCK-AR in rat pancreatic A and D cells remains poorly understood. The aim of this study was to identify the localization of CCK-AR in rat pancreatic islets by means of double immunofluorescence straining with antibodies against CCK-AR, glucagon, insulin and somatostatin and with in situ hybridization to detect its transcript. CCK-AR-like immunoreactive cells were found to overlap both with glucagon-like immunoreactive cells and insulin-like immunoreactive cells but not with somatostatin-like immunoreactive cells. An in situ hybridization study using a cRNA probe for CCK-AR revealed that CCK-AR mRNA was expressed in the center and periphery of the pancreatic islets. Further to this, immunofluorecsence staining using anti-glucagon antibody was carried out after in situ hybridization using the CCK-AR cRNA probe in order to identify CCK-AR mRNA expressing cells. CCK-AR mRNA exhibited a distribution pattern almost identical to that of glucagon-like immunoreactive cells. These results show clearly that CCK-AR exists not only in B but also in A cells of the rat pancreas, suggesting that CCK regulates the secretion of insulin and glucagon at least partly via CCK-AR.