ATP-sensitive potassium channel (K(ATP )channel) expression in the normal canine pancreas and in canine insulinomas

BACKGROUND: Pancreatic beta cells express ATP-sensitive potassium (K(ATP)) channels that are needed for normal insulin secretion and are targets for drugs that modulate insulin secretion. The K(ATP )channel is composed of two subunits: a sulfonylurea receptor (SUR 1) and an inward rectifying potassium channel (Kir(6.2)). K(ATP )channel activity is influenced by the metabolic state of the cell and initiates the ionic events that precede insulin exocytosis. Although drugs that target the K(ATP )channel have the expected effects on insulin secretion in dogs, little is known about molecular aspects of this potassium channel. To learn more about canine beta cell K(ATP )channels, we studied K(ATP )channel expression by the normal canine pancreas and by insulin-secreting tumors of dogs. RESULTS: Pancreatic tissue from normal dogs and tumor tissue from three dogs with histologically-confirmed insulinomas was examined for expression of K(ATP )channel subunits (SUR1 and Kir(6.2)) using RT-PCR. Normal canine pancreas expressed SUR1 and Kir(6.2 )subunits of the K(ATP )channel. The partial nucleotide sequences for SUR1 and Kir(6.2 )obtained from the normal pancreas showed a high degree of homology to published sequences for other mammalian species. SUR1 and Kir(6.2 )expression was observed in each of the three canine insulinomas examined. Comparison of short sequences from insulinomas with those obtained from normal pancreas did not reveal any mutations in either SUR1 or Kir(6.2 )in any of the insulinomas. CONCLUSION: Canine pancreatic K(ATP )channels have the same subunit composition as those found in the endocrine pancreases of humans, rats, and mice, suggesting that the canine channel is regulated in a similar fashion as in other species. SUR1 and Kir(6.2 )expression was found in the three insulinomas examined indicating that unregulated insulin secretion by these tumors does not result from failure to express one or both K(ATP )channel subunits

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The mean cell volume difference (dMCV) reflects serum hypertonicity in diabetic dogs.

Serum hypertonicity may develop during diabetes mellitus due to hyperglycemia and other biochemical changes. Hypertonicity may produce detrimental cellular and systemic effects and has been identified as a serum marker for some clinical disorders. In non-diabetic dogs, the mean cell volume difference, a novel erythrocyte measure, is increased by serum hypertonicity. However, it is not known whether hyperglycemic hypertonicity produces a similar change. The hypothesis that the mean cell volume difference could detect serum hypertonicity in diabetes was investigated in a group of thirty-two dogs with naturally-occurring diabetes mellitus that were prospectively recruited over a 1-year period from the outpatient population of a veterinary teaching hospital. The effect of hyperglycemia on the mean cell volume difference and the ability of the mean cell volume difference to predict serum hypertonicity were examined. Serum hyperosmolality and hypertonicity due to hyperglycemia was present in 91% and 94% of dogs, respectively. Hyperglycemia was the principal cause identified for serum hypertonicity and hyperosmolality. Using a cut-off value of ≥ 3 μm3 for the mean cell volume difference, serum hypertonicity ≥ 320 mmol/kg was identified with 79% sensitivity and 61% specificity. The dMCV correlated with changes in serum glucose, tonicity, and measured osmolality. Dogs with a mean cell volume difference ≥ 3 μm3 were at risk for serum tonicity ≥ 320 mmol/kg (risk ratio = 2.2) and serum glucose ≥ 13.9 mmol/L (risk ratio = 2.3). In conclusion, the mean cell volume difference is a useful surrogate marker for detecting serum hypertonicity in diabetic dogs and elevated mean cell volume difference is associated with increased risks for clinically relevant serum hypertonicity and hyperglycemia

Management and outcomes of isolated renal artery aneurysms in the endovascular era

OBJECTIVE: Isolated renal artery aneurysms are rare, and controversy remains about indications for surgical repair. Little is known about the impact of endovascular therapy on selection of patients and outcomes of renal artery aneurysms. METHODS: We identified all patients undergoing open or endovascular repair of isolated renal artery aneurysms in the Nationwide Inpatient Sample from 1988 to 2011 for epidemiologic analysis. Elective cases were selected from the period 2000 to 2011 to create comparable cohorts for outcome comparison. We identified all patients with a primary diagnosis of renal artery aneurysms undergoing open surgery (reconstruction or nephrectomy) or endovascular repair (coil or stent). Patients with concomitant aortic aneurysms or dissections were excluded. We evaluated patient characteristics, management, and in-hospital outcomes for open and endovascular repair, and we examined changes in management and outcomes over time. RESULTS: We identified 6234 renal artery aneurysm repairs between 1988 and 2011. Total repairs increased after the introduction of endovascular repair (8.4 in 1988 to 13.8 in 2011 per 10 million U.S. population; P = .03). Endovascular repair increased from 0 in 1988 to 6.4 in 2011 per 10 million U.S. population (P < .0001). However, there was no concomitant decrease in open surgery (5.5 in 1988 to 7.4 in 2011 per 10 million U.S. population; P = .28). From 2000 to 2011, there were 1627 open and 1082 endovascular elective repairs. Patients undergoing endovascular repair were more likely to have a history of coronary artery disease (18% vs 11%; P < .001), prior myocardial infarction (5.2% vs 1.8%; P < .001), and renal failure (7.7% vs 3.3%; P < .001). In-hospital mortality was 1.8% for endovascular repair, 0.9% for open reconstruction (P = .037), and 5.4% for nephrectomy (P < .001 compared with all revascularization). Complication rates were 12.4% for open repair vs 10.5% for endovascular repair (P = .134), including more cardiac (2.2% vs 0.6%; P = .001) and peripheral vascular complications (0.6% vs 0.0%; P = .014) with open repair. Open repair had a longer length of stay (6.0 vs 4.6 days; P < .001). After adjustment for other predictors of mortality, including age (odds ratio [OR], 1.05 per decade; 95% confidence interval [CI], 1.0-1.1; P = .001), heart failure (OR, 7.0; 95% CI, 3.1-16.0; P < .001), and dysrhythmia (OR, 5.9; 95% CI, 2.0-16.8; P = .005), endovascular repair was still not protective (OR, 1.6; 95% CI, 0.8-3.2; P = .145). CONCLUSIONS: More renal artery aneurysms are being treated with the advent of endovascular techniques, without a reduction in operative mortality or a reduction in open surgery. Indications for repair of renal artery aneurysms should be re-evaluated