At last, a weight neutral insulin?

Fritsche, Andreas; Häring, Hans Ulrich

doi:10.1038/sj.ijo.0802749

Cited by 56 publications

(34 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Indeed, it has already been shown that after intranasal administration the rapid-acting insulin analogue aspart exerts a stronger effect on improvement of memory performance than regular human insulin [26]. Also, clinical studies indicate that insulin detemir in comparison with other long-acting insulins attenuates weight gain in type 2 diabetic patients, as summarised [47]. Because of its acylation with a fatty acid, detemir is assumed to have facilitated access to the brain due to enhanced BBB transport.…”

Section: Therapeutic Perspectivesmentioning

confidence: 99%

Central nervous insulin resistance: a promising target in the treatment of metabolic and cognitive disorders?

Hallschmid

Schultes

2009

Diabetologia

View full text Add to dashboard Cite

Research on functions and signalling pathways of insulin has traditionally focused on peripheral tissues such as muscle, fat and liver, while the brain was commonly believed to be insensitive to the effects of this hormone secreted by pancreatic beta cells. However, since the discovery some 30 years ago that insulin receptors are ubiquitously found in the central nervous system, an evergrowing research effort has conclusively shown that circulating insulin accesses the brain, which itself does not synthesise insulin, and exerts pivotal functions in central nervous networks. As an adiposity signal reflecting the amount of body fat, insulin provides direct negative feedback to hypothalamic nuclei that control whole-body energy and glucose homeostasis. Moreover, insulin affects distinct cognitive processes, e.g. by triggering the formation of psychological memory contents. Accordingly, metabolic and cognitive disorders such as obesity, type 2 diabetes mellitus and Alzheimer's disease are associated with resistance of central nervous structures to the effects of insulin, which may derive from genetic polymorphisms as well as from long-term exposure to excess amounts of circulating insulin due to peripheral insulin resistance. Thus, overcoming central nervous insulin resistance, e.g. by pharmacological interventions, appears to be an attractive strategy in the treatment and prevention of these disorders. Enhancement of central nervous insulin signalling by administration of intranasal insulin, insulin analogues and insulin sensitisers in basic research approaches has yielded encouraging results that bode well for the successful translation of these effects into future clinical practice.

show abstract

Section: Therapeutic Perspectivesmentioning

confidence: 99%

Central nervous insulin resistance: a promising target in the treatment of metabolic and cognitive disorders?

Hallschmid

Schultes

2009

Diabetologia

View full text Add to dashboard Cite

show abstract

“…Over the past years data have accumulated supporting the fact that insulin therapy using insulin detemir leads to both improved glycaemic control and weight stability [14], opening new perspectives for insulin therapy. However, the mechanism(s) underlying the altered weight gain with insulin detemir are unknown.…”

Section: Introductionmentioning

confidence: 99%

Tissue selectivity of insulin detemir action in vivo

et al. 2006

View full text Add to dashboard Cite

Aims/hypothesis: Recombinant DNA technology is a useful tool that can be used to create insulin analogues with modified absorption kinetics to improve glycaemic control in patients with type 1 and type 2 diabetes. Among conventional insulin analogues, which are usually created by amino acid exchange, insulin detemir is the first analogue to be acylated with a fatty acid to enable reversible albumin binding. In this study we determined activation of the insulin receptor (IR)-signalling cascade by insulin detemir at the level of IR and IR substrate (Irs) phosphorylation, as well as downstream signalling elements such as phosphatidylinositol 3-kinase and Akt, and performed epidural EEG in vivo. Methods: C57Bl/6 mice were injected i.v. with either insulin detemir or human insulin and Western blot analysis was performed on liver, muscle, hypothalamic and cerebrocortical tissues. Moreover, cerebrocortical activity was detected by EEG in awake mice and cerebral insulin concentrations were measured following human insulin and insulin detemir injection. Results: The time course and extent of IR phosphorylation in peripheral tissues were similar following insulin detemir treatment compared with human insulin, but insulin signalling in hypothalamic and cerebrocortical tissue determined by tyrosine-phosphorylation of the IR and Irs2 proteins occurred faster and was enhanced due to a higher insulin detemir concentration in the brain. Moreover, epidural EEG in mice displayed increased cortical activity using insulin detemir. Conclusions/interpretation: Taken together, these data suggest that insulin detemir has a tissue-selective action, with a relative preference for brain compared with peripheral tissues.

show abstract

“…This finding is in contrast to NPH insulin, which was associated with weight gain of 0.7 to 0.8 kg over 6 months [41][42][43][44][45] 48 There was also a risk reduction for nocturnal hypoglycemia of some 50% with insulin detemir in this study. It is possible that the reduced risk of weight gain with insulin detemir might relate to the risk reduction for hypoglycemia, but other mechanisms, including a reduced ratio of peripheral:hepatic action 49 and a central effect on appetite, 50 have been suggested.…”

Section: Insulin Detemirmentioning

confidence: 99%

Consequences of Weight Gain Associated With Insulin Therapy in Adolescents

Kaufman¹

2006

The Endocrinologist

View full text Add to dashboard Cite

Abstract:Intensive insulin therapy is associated with the delayed onset and reduced risk of the development of microvascular complications in type 1 diabetes and is therefore recommended for most patients, including children and adolescents. Intensification of insulin therapy can be accompanied by increased weight gain, and fear of weight gain can represent a major barrier to adherence to intensive regimens. This is particularly true for adolescent girls who may have poor self-esteem and body image issues, and adopt behaviors such as insulin omission and disordered eating to prevent weight gain. Strategies to reduce insulin-associated weight gain include lifestyle interventions to improve nutritional intake and increase physical activity. The use of pharmacologic agents that minimize weight gain such as the inclusion of insulin detemir, agents that alter satiety and insulin sensitizers should also be considered and investigated further. In addition to understanding treatment strategies to limit insulin-related weight gain, the diabetes healthcare team should be aware of the early warning signs of disordered eating and insulin omission in the adolescent so that appropriate referral for psychologic intervention can occur.

show abstract

At last, a weight neutral insulin?

Cited by 56 publications

References 34 publications

Central nervous insulin resistance: a promising target in the treatment of metabolic and cognitive disorders?

Central nervous insulin resistance: a promising target in the treatment of metabolic and cognitive disorders?

Tissue selectivity of insulin detemir action in vivo

Consequences of Weight Gain Associated With Insulin Therapy in Adolescents

Contact Info

Product

Resources

About