Insulin: understanding its action in health and disease

Sönksen, Peter H.; Sonksen, Julian

doi:10.1093/bja/85.1.69

Cited by 164 publications

(115 citation statements)

References 4 publications

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“…At low concentrations of insulin, the glucose lowering effect occurs mainly by suppression of glucose R a , with only a small effect on glucose R d . At higher concentrations the majority of action occurs by glucose R d once glucose R a has effectively been completely suppressed [20]. Therefore results from studies comparing the effects of two insulin preparations on glucose R a and R d under circumstances in which the glucose infusion profile is not equivalent must be treated with caution as differences in effect may be purely related to dose.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the effects on glucose and lipid metabolism of equipotent doses of insulin detemir and NPH insulin with a 16-h euglycaemic clamp

et al. 2005

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Aims/hypothesis: The association of insulin detemir with non-esterified fatty acid binding sites on albumin may limit its transfer from the circulation into the extravascular extracellular space in adipose tissue and muscle, due to the capillary endothelial cell barrier. In the liver, the open sinusoids may expose hepatocytes to insulin detemir, enabling it to have a greater effect in the liver than in peripheral tissues. Methods: We investigated the effects of equipotent doses of insulin detemir and NPH insulin on hepatic glucose rate of appearance (R a ), peripheral glucose rate of disposal (R d ) and glycerol R a (a measure of lipolysis) using stable isotope techniques. We also investigated the effects of these insulins on NEFA concentrations in seven healthy volunteers during a 16-h euglycaemic clamp. A higher dose of insulin detemir was also studied. Results: There was no difference in the glucose infusion profile between insulin detemir and NPH. Insulin detemir had a greater effect on mean suppression of glucose R a (mean difference 0.24 mg kg −1 min −1; CI 0.09-0.39; p<0.01), and minimum glucose R a , with minimum low dose detemir −0.10±0.15 mg·kg −1 ·min −1 and minimum NPH 0.17±0.10 mg·kg −1 ·min −1 (p<0.02). However, it had a lesser effect on mean suppression of NEFA concentrations (mean difference −0.10 mmol/l; CI −0.03 to −0.17; ANOVA, p<0.02) than NPH. The effect of insulin detemir on glucose R d and glycerol R a was not different from NPH. Following high-dose detemir, total glucose infused and maximum glucose R d were higher (p<0.02, p<0.03) and plasma NEFA concentrations lower (p<0.01) than with low-dose determir. Conclusions/interpretation: This study suggests that insulin detemir, when compared to NPH insulin, has a greater effect on the liver than on peripheral tissues and thus has the potential to restore the physiological insulin gradient.

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Section: Discussionmentioning

confidence: 99%

Comparison of the effects on glucose and lipid metabolism of equipotent doses of insulin detemir and NPH insulin with a 16-h euglycaemic clamp

et al. 2005

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“…Despite a wealth of evidence confirming these early studies, this 'new concept' of insulin action remains unrecognised by the majority of teachers of physiology and biochemistry. A remarkable example of how difficult it sometimes is to reverse dogma even when it has been proven to be wrong (Sonksen & Sonksen 2000).…”

Section: Autacoids -Excitatory Substances Chalones -Inhibitory Substamentioning

confidence: 99%

Insulin, growth hormone and sport

Sönksen

2001

Journal of Endocrinology

171

145

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This review examines some interesting 'new' histories of insulin and reviews our current understanding of its physiological actions and synergy with GH in the regulation of metabolism and body composition. It reviews the history of GH abuse that antedates by many years the awareness of endocrinologists to its potent anabolic actions. Promising methods for detection of GH abuse have been developed but have yet to be sufficiently well validated to be ready for introduction into competitive sport. So far, there are two promising avenues for detecting GH abuse. The first uses immunoassays that can distinguish the isomers of pituitary-derived GH from the monomer of recombinant human GH. The second works through demonstrating circulating concentrations of one or more GH-sensitive substances that exceed the extremes of normal physiological variability. Both methods require blood rather than urine samples. The first method has a window of opportunity lasting about 24 h after an injection and is most suitable for 'out of competition' testing. The second method has reasonable sensitivity for as long as 2 weeks after the last injection of GH and is uninfluenced by extreme exercise and suitable for post-competition samples. This method has a greater sensitivity in men than in women. The specificity of both methods seems acceptably high but lawyers need to decide what level of scientific probability is needed to obtain a conviction. Both methods need further validation before implementation. Research work carried out as part of the fight against doping in sport has opened up a new and exciting area of endocrinology.

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“…Insulin controls glucose output by the liver and activates glucose transporters, enabling cells to uptake glucose from the blood to be metabolized in the Krebs cycle and/or glycolysis for ATP production in the mitochondria [8,9]. Consequentially, a lack of insulin or deficient insulin signaling deregulates energy metabolism, and one key biomarker as well as a hallmark of diabetes is elevated BGL [10].…”

Section: Introductionmentioning

confidence: 99%

Sirt1-Independent Rescue of Muscle Regeneration by Resveratrol in Type I Diabetes

Conboy¹

2013

J Diabetes Metab

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Insulin: understanding its action in health and disease

Cited by 164 publications

References 4 publications

Comparison of the effects on glucose and lipid metabolism of equipotent doses of insulin detemir and NPH insulin with a 16-h euglycaemic clamp

Comparison of the effects on glucose and lipid metabolism of equipotent doses of insulin detemir and NPH insulin with a 16-h euglycaemic clamp

Insulin, growth hormone and sport

Sirt1-Independent Rescue of Muscle Regeneration by Resveratrol in Type I Diabetes

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