Insulin Sensitizer

Alzheimer’s disease (AD) is associated with insulin resistance and specific regional declines in cerebral metabolism. The effects of a novel mTOT modulating insulin sensitizer (MSDC-0160) were explored in non-diabetic patients with mild AD to determine whether treatment would impact glucose metabolism measured by FDG-PET in regions that decline in AD. MSDC-0160 (150 mg once daily; N=16) compared to placebo (N=13) for 12 weeks did not result in a significant difference in glucose metabolism in pre-defined regions when referenced to the pons or whole brain. However, glucose metabolism referenced to cerebellum was maintained in MSDC-0160 treated participants while it significantly declined for placebo patients in anterior and posterior cingulate, and parietal, lateral temporal, medial temporal cortices. Voxel-based analyses showed additional differences in FDG-PET related to MSDC-0160 treatment. These exploratory results suggest central effects of MSDC-0160 and provide a basis for further investigation of mTOT modulating insulin sensitizers in AD patients.

Objective:The objective of the present study was to investigate the
insulin sensitizing effect of  Scoparia dulcis(L) leave extract (SDE)
against free fatty acid (FFA) induced insulin resistance in an  in vitro
L6 myotubes.
Materials  and  Methods: The  rat  L6  skeletal  muscle  cells  were
differentiated to myotubes by treating it with DMEMcontaining 2%
horse  serum  for  12h.  For  generating  an  in  vitro cellular  model  of
insulin  resistant  condition,  L6  myotubes  were  treated  with  FFA
(palmitate) for 4h. Insulin resistant L6 myotubes were either pre- or
post treated for 1h with SDE and its insulin sensitivity activity was
assessed  by  measuring  cellular  glucose  uptake  and  the  activation
status of insulin signalling pathway molecules.
Results: SDE  significantly  stimulated  glucose  uptake  in  L6
myotubes  in  a  dose-dependent  manner  with  maximal  effect  at
50µg/ml. To investigate the underlying mechanism ofeffect SDE, we
examined  the  expression  and  activity  of  insulin  signalling  pathway
molecules.  We  found  that  the  SDE  treatment  notably  increased
insulin  signalling  pathway  by  inducing  activatory  phosphorylation
status  of  IRS-1  and  Akt  without  altering  expression levels  of  these
proteins. The comparative analysis revealed that SDE is more potent
than known insulin sensitizer, pioglitazone.
Conclusion:These results suggest that induction of insulin signalling
pathway and increased glucose uptake activity of SDE will aid in the
treatment of insulin resistance and type 2 diabetes. Future studies on
the isolation of bioactive components and a detailed investigation in
the animal model of insulin resistance may be promising to find out a
novel type 2 diabetes drug.