KATP Channels and Pancreatic Islet Blood Flow in Anesthetized Rats

Abstract

K ATP channels are important for insulin secretion and depolarization of vascular smooth muscle. In view of the importance of drugs affecting K ATP channels in the treatment of diabetes, we investigated the effects of these channels on splanchnic blood perfusion in general and pancreatic islet blood flow in particular. We treated anesthetized Sprague-Dawley rats with the K ATP channel openers diazoxide or NNC 55-0118 or the K ATP channel closer glipizide. Both diazoxide and NNC 55-0118 dose-dependently increased total pancreatic and islet blood flow in the presence of moderate hyperglycemia, but had no effects on the blood perfusion of other splanchnic organs. Diazoxide markedly lowered the mean arterial blood pressure and thus increased vascular conductance in all organs studied. NNC 55-0118 had much smaller effects on the blood pressure. Glipizide did not affect total pancreatic blood flow, but decreased islet blood flow by 50% in the presence of hypoglycemia. We conclude that K ATP channels actively participate in the blood flow regulation of the pancreatic islets and that substances affecting such channels may also influence islet blood flow.

Novel and Established Potassium Channel Openers Stimulate Hair Growth In Vitro: Implications for their Modes of Action in Hair Follicles

“…Indeed, minoxidil sulfate exhibits a biphasic affinity for Kir6.2/SUR2B channels (Schwanstecher et al, 1998). On the other hand, the growth stimulation elicited by the novel, channel-specific, potassium channel opener, NNC 55-0118 (Nielsen et al, 2002;Dabrowski et al, 2003;Jansson et al, 2003), indicates an effect mediated through SUR1/Kir6.2 potassium channels. The inhibitory effects of tolbutamide both alone, and opposing the action of NNC 55-0118, also supports an action through SUR1/Kir6.2 potassium channels as tolbutamide has a high affinity for the SUR1 receptor.…”

“…Therefore, isolated red deer anagen follicles cultured in serum-free media in the absence of streptomycin were investigated to examine their potential as a bioassay for the assessment of hair growth-promoting drugs and to elucidate further the mode of action of potassium channel openers on hair growth. The effects of the established potassium channel openers, minoxidil and diazoxide, and a new drug, NNC 55-0118 (NovoNordisk, Bagsvaed, Denmark) (Nielsen et al, 2002;Dabrowski et al, 2003;Jansson et al, 2003), on the rate of follicular growth were compared. NNC 55-0118 only opens Kir6.2/SUR1channels (Nielsen et al, 2002;Dabrowski et al, 2003).…”

Flow distribution during infusion of UW and HTK solution in anaesthetised rats

“…This may be due to the high potassium concentrations, to which the islets may be more sensitive, analogous to what we have seen when evaluating the role of K ATP channels in islet blood flow regulation [27]. Substances which open K ATP channels in beta cells, e. g. diazoxide, induce not only 'beta-cell rest', which in itself may be advantageous during islet isolation [28], but also increase islet blood flow [27]. Thus, addition of such drugs to preservation solutions would be of interest to evaluate if this might increase the yield of islets during subsequent isolation by preferentially increasing the preservation solution flow through the islets.…”

“…presumably reduced their perfusion, when compared to HTK or Ringer solution. This may be due to the high potassium concentrations, to which the islets may be more sensitive, analogous to what we have seen when evaluating the role of K ATP channels in islet blood flow regulation [27]. Substances which open K ATP channels in beta cells, e. g. diazoxide, induce not only 'beta-cell rest', which in itself may be advantageous during islet isolation [28], but also increase islet blood flow [27].…”

Diazoxide Increases Liver and Kidney HSP25 and HSP70 After Shock and Stroke

“…administration of DZ (3.2 mg/kg infusion over 10 min) did not alter mean arterial pressure during or immediately after infusion. Jansson [40] reported that plasma glucose levels are elevated 20 min after 10 -30 mg/kg i.v. administration, and we found that by ϳ95 min after 3.2 mg/kg i.v.…”