guest ::
| Home > Publications Database > 738 Insulin action in the brain depends on whole-body insulin sensitivity |
| Home > Publications Database > 738 Insulin action in the brain depends on whole-body insulin sensitivity |
| Abstract/Journal Article | DZNE-2020-00869 |
;
2013
Abstract: Background and aims: Insulin action in the brain determines food intake, physical activity and finally glucose homeostasis. In particular, insulin im-proved brain activity and promoted locomotion in lean humans and mice while obese individuals are characterized by impaired insulin action in the brain and physical inactivity. As insulin enters the brain in a receptor-medi-ated fashion, we hypothesized that whole body insulin resistance might af-fect the transport of insulin into the brain with impacts on brain activity and locomotion.Materials and methods: In mice, insulin was applied for four consecutive days by subcutaneous injection (1 unit/kg body weight), and assessment of cortical activity and locomotion in whole-body insulin-sensitive and -resist-ant C57BL/6 mice were performed by radiotelemetry recordings. Moreover, twenty-two healthy human subjects participated in an oral glucose tolerance testing (oGTT) to determine whole body insulin sensitivity and underwent lumbar puncture to measure insulin and glucose concentrations in the cer-ebrospinal fluid (CSF).Results: Subcutaneous insulin injection on four consecutive days did not affect blood glucose or body weight. In insulin-sensitive mice, brain activ-ity was significantly increased in the theta, alpha and beta frequency bands (theta: by 10.0±2.8%; alpha: by 12.3±2.0%; beta: by 11.7±1.4%; P<0.05; n=10/group) while this was not present in insulin-resistant animals. In addition, lo-comotor activity was significantly increased by 32.4±3.7% (P<0.001) during the insulin treatment period in insulin-sensitive mice but not in those with insulin resistance. Interestingly, when insulin was intracerebroventricularly applied into insulin-resistant animals it increased brain activity in abovemen-tioned frequency bands (alpha: by 18.9±3.5%; beta: by 11.1±2.0%; P<0.005; n=8/group). In humans, blood and CSF concentrations of glucose and insulin were significantly correlated (glucose: P=0.008; insulin: P=0.021). The CSF/serum ratio for insulin was significantly associated with whole body insulin sensitivity (P=0.01, r2=0.4) with reduced insulin transported into the CSF in insulin-resistant subjects, while this was not true for glucose (P=0.3).Conclusion: Physiological doses of insulin improve brain activity and lo-comotion in insulin-sensitive mice. However, impaired transport of insulin across the blood-brain-barrier (BBB) contributes to the absent response in insulin-resistant animals which can be in part overcome by an intracer-ebroventricular injection. This is well in line with our human data where in-sulin transport into the CSF was impaired in whole-body insulin-resistant subjects. Together, our data point toward a major contribution of insulin re-sistance at the BBB in the pathophysiology of brain insulin resistance. This underlines the need for sensitizing measures accompanying insulin therapy in insulin resistant patients.
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Springer ; Essential Science Indicators ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz
; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection
|
The record appears in these collections: |
