Alfalfa-derived HSP70 administered intranasally improves insulin sensitivity in mice

Abstract

Heat shock protein (HSP) 70 is an abundant cytosolic chaperone protein that is deficient in insulin-sensitive tissues in diabetes and unhealthy aging, and is considered a longevity target. It is also protective in neurological disease models. Using HSP70 purified from alfalfa and administered as an intranasal solution, we tested in whether the administration of Hsp70 to diet-induced diabetic mice would improve insulin sensitivity. Both the 10 and 40 μg given three times per week for 26 days significantly improved the response to insulin. The HSP70 was found to pass into the olfactory bulbs within 4-6 hours of a single dose. These results suggest that a relatively inexpensive, plentiful source of HSP70 administered in a simple, non-invasive manner, has therapeutic potential in diabetes.

<p>Chaperone-Based Therapeutic Target Innovation: Heat Shock Protein 70 (HSP70) for Type 2 Diabetes Mellitus</p>

“…Nonetheless, based on previous research, it is known that increased expression of HSP70 on olfactory bulb, hippocampus, and hypothalamus happened simultaneously with increased insulin sensitivity on peripheral tissues. 15 This supports the hypothesis regarding the increased expression of HSP70 on the brain to affect insulin sensitivity, both on brain and peripheral tissues.…”

“…Intranasally administered HSP70 will experience uptake through nasal epithelia, then proceed to glomerular from the olfactory bulb. 15 Past findings explained a hypothesis that the uptake mechanism and the distribution were similar to albumin if observed from its molecular structure. The distribution of albumin happens in whole-brain parts through the transcytosis mechanism.…”

“…Therefore, there is no difference in its function. 15 A study done by Tytell et al examined aHSP70 in DM rats and the result shows a decreased level of HbA1C by 0.1%. The outcome itself was not significant statistically due to the lack of sample size used and the short duration for the study which was only for 32 days.…”

“…Strategies targeting HSP70 modulation in T2DM (longterm physical exercise, HTT, and aHSP70) are capable of maintaining and increasing the expression of HSP70, hence preventing the progression towards more severe T2DM. [13][14][15]58,59 Several studies have shown its capability to restore insulin sensitivity. 13 Therefore, though many of its roles, HSP70 has the promising potency to become the therapeutic target in managing T2DM.…”

“…Those interventions include long-term physical exercise, hot tub therapy (HTT), and administration of alfalfa-derived HSP70 (aHSP70). [13][14][15] Further understanding regarding HSP70 role in T2DM pathogenesis may disclose new possibilities to modulate HSP70 in the future. Therefore, the authors are interested in reviewing deeper regarding HSP70 role in T2DM pathogenesis and its role as innovation for therapy target in T2DM patients.…”