Abstract
Treatment of primary cultured adipocytes with 50 ng/ml insulin and 20 mM glucose for 0-6 h resulted in a loss of maximal insulin responsiveness (MIR) which was immediate (no lag period), rapid (t1/2 of 3 h), linear, and extensive (80% of that seen at 24 h), whereas loss of insulin sensitivity from 0-24 h was slow (t1/2 = 8 h), extensive (insulin ED50 of 0.3 and 1.45 ng/ml at 2 and 24 h, respectively), and was preceded by an initial 2-h lag. Recovery of MIR and insulin sensitivity was assessed by inducing desensitization for various times from 2-24 h, removing insulin and glucose, and then measuring MIR and insulin sensitivity over a subsequent 1-6-h period. After 2 h, recovery of MIR in desensitized cells was rapid (251 pmol of glucose/3 min/h), whereas after 24 h, recovery was much slower (35 pmol/3 min/h). In contrast, the opposite trend was seen for recovery of insulin sensitivity: at early times recovery of insulin sensitivity was slow (0.05 ng/ml/h) but was rapid after 24 h (0.12 ng/ml/h). Thus, it appears that MIR and insulin sensitivity can be independently regulated since recovery rates for MIR and insulin sensitivity diverged with the progression of insulin resistance. When the effects of insulin and glucose on recovery were examined, we found that insulin alone was unable to block recovery of MIR or insulin sensitivity. Glucose alone, however, was effective in preventing recovery of insulin sensitivity but not recovery of MIR. In the presence of 20 mM glucose, low doses of insulin (treatment EC50 = 0.22-0.46 ng/ml) effectively prevented recovery of both MIR and insulin sensitivity. De novo protein synthesis apparently is not involved in the development of insulin resistance or the reversal of desensitization since inhibition of protein synthesis by cycloheximide had no effect on the loss of MIR and insulin sensitivity or recovery.(ABSTRACT TRUNCATED AT 400 WORDS)
Highlights
Desensitization of peripheral target tissues to thebiological actions of insulin is the hallmark of certain pathophysiological states such as Type I1 diabetes and obesity and is characterized byimpaired insulin action that is manifested by decreased insulin responsiveness and/or insulin sensitivity [1,2,3,4,5,6]. the cellular and molecular mechanisms underlying insulin resistance have not been fully elucidated, recent advances have provided important new insights into this process
Involved in the development of insulin resistance or As exemplified by the above studies, isolated rat adipocytes the reversalof desensitization since inhibitionof pro- are ideally suited for investigating the cellular mechanisms tein synthesis by cycloheximide had no effect on the underlying insulin resistance of the glucose transport system
We have examined the other arm of insulin resistance, namely, recovery of insulin action after in uptake of hexose by simple diffusion and nonspecific trapping of radioactivity in the cell pellet, we assessed glucose uptake in the presence of 0.3 mM phloretin [19]
Summary
That observed in deactivated and insulin-restimulated cells. ,deactivation of the glucose transportsystemisnot. After oughly washing the cellsin cold (10 "C) insulin-free and thoroughly washing the cells (control and desensitized), we glucose-free buffer, we determined the MIR of the glucose determined the insulin sensitivity of the glucose transport transport systemby acutely restimulatingcells with 25 ng/ml system a t each of the indicatedtimes. This wasaccomplished insulin and measuring the2-deoxyglucose uptake rates. Identical sensitivity was characterized by a n initial 2-h lag period in results were obtained when glucose transport was assessed which little or no change in sensitiviwtyas observed (ED50of using radiolabeled 3-0-methylglucose (4a0% decrease in MIR 0.26 versus 0.30 ng/ml at 0 and 2 h, respectively).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
