Effect of insulin-induced hypoglycaemia on the peripheral nervous system: focus on adaptive mechanisms, pathogenesis and histopathological changes

TY - JOUR

T1 - Effect of insulin-induced hypoglycaemia on the peripheral nervous system

T2 - focus on adaptive mechanisms, pathogenesis and histopathological changes

AU - Jensen, Vivi Flou Hjorth

AU - Mølck, A.-M.

AU - Bøgh, I. B.

AU - Lykkesfeldt, Jens

N1 - © 2014 British Society for Neuroendocrinology.

PY - 2014/8

Y1 - 2014/8

N2 - Insulin-induced hypoglycaemia (IIH) is a common acute side effect in type 1 and type 2 diabetic patients, especially during intensive insulin therapy. The peripheral nervous system (PNS) depends on glucose as its primary energy source during normoglycaemia and, consequently, it may be particularly susceptible to IIH damage. Possible mechanisms for adaption of the PNS to IIH include increased glucose uptake, utilisation of alternative energy substrates and the use of Schwann cell glycogen as a local glucose reserve. However, these potential adaptive mechanisms become insufficient when the hypoglycaemic state exceeds a certain level of severity and duration, resulting in a sensory-motor neuropathy with associated skeletal muscle atrophy. Large myelinated motor fibres appear to be particularly vulnerable. Thus, although the PNS is not an obligate glucose consumer, as is the brain, it appears to be more prone to IIH than the central nervous system when hypoglycaemia is not severe (blood glucose level ≤ 2 mm), possibly reflecting a preferential protection of the brain during periods of inadequate glucose availability. With a primary focus on evidence from experimental animal studies investigating nondiabetic IIH, the present review discusses the effect of IIH on the PNS with a focus on adaptive mechanisms, pathogenesis and histological changes.

AB - Insulin-induced hypoglycaemia (IIH) is a common acute side effect in type 1 and type 2 diabetic patients, especially during intensive insulin therapy. The peripheral nervous system (PNS) depends on glucose as its primary energy source during normoglycaemia and, consequently, it may be particularly susceptible to IIH damage. Possible mechanisms for adaption of the PNS to IIH include increased glucose uptake, utilisation of alternative energy substrates and the use of Schwann cell glycogen as a local glucose reserve. However, these potential adaptive mechanisms become insufficient when the hypoglycaemic state exceeds a certain level of severity and duration, resulting in a sensory-motor neuropathy with associated skeletal muscle atrophy. Large myelinated motor fibres appear to be particularly vulnerable. Thus, although the PNS is not an obligate glucose consumer, as is the brain, it appears to be more prone to IIH than the central nervous system when hypoglycaemia is not severe (blood glucose level ≤ 2 mm), possibly reflecting a preferential protection of the brain during periods of inadequate glucose availability. With a primary focus on evidence from experimental animal studies investigating nondiabetic IIH, the present review discusses the effect of IIH on the PNS with a focus on adaptive mechanisms, pathogenesis and histological changes.

KW - Faculty of Health and Medical Sciences

KW - Insulin

KW - Hypoglycaemia

KW - glucose transporters

KW - peripheral neuropathy

KW - axonal degeneration

KW - skeletal muscle atrophy

U2 - 10.1111/jne.12170

DO - 10.1111/jne.12170

M3 - Journal article

C2 - 24921897

SN - 0953-8194

VL - 26

SP - 482

EP - 496

JO - Journal of Neuroendocrinology

JF - Journal of Neuroendocrinology

IS - 8

ER -