The effects of KATP channel modulators on counterregulatory responses and cognitive function during acute controlled hypoglycaemia in healthy men: a pilot study

Bingham, Emma; Hopkins, David; Pernet, A; Reid, H. L.; Macdonald, Ian A.; Amiel, Stephanie A.

doi:10.1046/j.1464-5491.2003.00922.x

Cited by 20 publications

(26 citation statements)

References 34 publications

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“…Diazoxide, given orally, suppressed basal C-peptide and suppressed the glucagon response to hypoglycemia induced 2 h later while having no effect on epinephrine, norepinephrine, or neurogenic symptoms (41). Similarly, Bingham et al (42) reported no effect of oral diazoxide (5 mg/kg) on the hormonal counterregulatory response in 10 nondiabetic humans. In our rodent study, diazoxide given intravenously 30 min before hypoglycemia also suppressed C-peptide but resulted in an amplified epinephrine response during hypoglycemia.…”

Section: Discussionmentioning

confidence: 94%

Amplified Hormonal Counterregulatory Responses to Hypoglycemia in Rats After Systemic Delivery of a SUR-1–Selective K+ Channel Opener?

et al. 2008

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1OBJECTIVE-In glucose-sensing neurons, ATP-sensitive K ϩ channels (K ATP channels) are thought to translate metabolic signals into an alteration in neuronal firing rates. Because these neurons express the Kir6.2/SUR-1 isoform of the K ATP channel, we sought to examine the therapeutic potential of the SUR-1-selective potassium channel opener (KCO), NN414, to amplify counterregulatory response to hypoglycemia. RESEARCH DESIGN AND METHODS-In vivo dose-response studies with NN414 delivered intravenously to normal Sprague-Dawley rats before the induction of controlled hypoglycemia were performed. Based on these studies, the potential for NN414 to restore counterregulatory responses in chronically cannulated nondiabetic and diabetic BB rats was explored using the in vivo hyperinsulinemic-hypoglycemic clamp technique. RESULTS-NN414delivered systemically amplified epinephrine responses during acute hypoglycemia and showed a persisting effect to amplify the epinephrine response when given 24 h before the hypoglycemic study. Local delivery of a potassiumchannel blocker to the ventromedial hypothalamus reversed the effects of systemic NN414. In addition, NN414 amplified the epinephrine response to hypoglycemia in both nondiabetic and diabetic BB rats with defective hormonal counterregulation.CONCLUSIONS-These studies demonstrate in a variety of rodent models that systemic delivery of Kir6.2/SUR-1-selective KCOs enhance the glucose counterregulatory response to insulin-induced hypoglycemia. Future studies in human subjects are now required to determine their potential as a therapy for hypoglycemia-associated autonomic failure in type 1 diabetes.

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Section: Discussionmentioning

confidence: 94%

Amplified Hormonal Counterregulatory Responses to Hypoglycemia in Rats After Systemic Delivery of a SUR-1–Selective K+ Channel Opener?

et al. 2008

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“…Bingham et al (43) found no significant effect of diazoxide on the glucagon response to hypoglycemia in healthy men, although the mean peak glucagon concentration tended to be lower after diazoxide than after placebo administration. However, they used a lower dosage of diazoxide and did not document an effect of the drug on insulin secretion by measuring plasma C-peptide concen- Data are means Ϯ SE.…”

Section: Discussionmentioning

confidence: 99%

Loss of the Decrement in Intraislet Insulin Plausibly Explains Loss of the Glucagon Response to Hypoglycemia in Insulin-Deficient Diabetes

2005

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“…Finger tapping test A computer key was pressed as many times as possible for 10 s. The test was repeated three times at each defined time-point and the mean calculated [10].…”

Section: Methodsmentioning

confidence: 99%

Differential effects of insulin detemir and neutral protamine Hagedorn (NPH) insulin on hepatic glucose production and peripheral glucose uptake during hypoglycaemia in type 1 diabetes

et al. 2009

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Aims/hypothesis We compared the symptoms of hypoglycaemia induced by insulin detemir (NN304) (B29Lys(ε-tetradecanoyl),desB30 human insulin) and equally effective doses of neutral protamine Hagedorn (NPH) insulin in relation to possible differential effects on hepatic glucose production and peripheral glucose uptake. Methods After overnight intravenous infusion of soluble human insulin 18 participants with type 1 diabetes received subcutaneous injections of NPH insulin or insulin detemir (0.5 U/kg body weight) on separate occasions in random order. During the ensuing gradual development of hypoglycaemia cognitive function and levels of counter-regulatory hormones were measured and rates of endogenous glucose production and peripheral glucose uptake continuously evaluated using a primed constant infusion of [6,6-2 H 2 ] glucose. The study was terminated when plasma glucose concentration had fallen to 2.4 mmol/l or had reached a minimum at a higher concentration. Results During the development of hypoglycaemia no difference between the two insulin preparations was observed in symptoms or hormonal responses. Significant differences were seen in rates of glucose flux. At and below plasma glucose concentrations of 3.5 mmol/l suppression of endogenous glucose production was greater with insulin detemir than with NPH insulin, whereas stimulation of peripheral glucose uptake was greater with NPH insulin than with insulin detemir. Conclusions/interpretation In participants with type 1 diabetes subcutaneously injected insulin detemir exhibits relative hepatoselectivity compared with NPH insulin, but symptoms of hypoglycaemia and hormonal counterregulation are similar.

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The effects of KATP channel modulators on counterregulatory responses and cognitive function during acute controlled hypoglycaemia in healthy men: a pilot study

Cited by 20 publications

References 34 publications

Amplified Hormonal Counterregulatory Responses to Hypoglycemia in Rats After Systemic Delivery of a SUR-1–Selective K+ Channel Opener?

Amplified Hormonal Counterregulatory Responses to Hypoglycemia in Rats After Systemic Delivery of a SUR-1–Selective K+ Channel Opener?

Loss of the Decrement in Intraislet Insulin Plausibly Explains Loss of the Glucagon Response to Hypoglycemia in Insulin-Deficient Diabetes

Differential effects of insulin detemir and neutral protamine Hagedorn (NPH) insulin on hepatic glucose production and peripheral glucose uptake during hypoglycaemia in type 1 diabetes

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