Chlorogenic Acid Stimulates Glucose Transport in Skeletal Muscle via AMPK Activation: A Contributor to the Beneficial Effects of Coffee on Diabetes

Chlorogenic acid (CGA) has been shown to delay intestinal glucose absorption and inhibit gluconeogenesis. Our aim was to investigate the role of CGA in the regulation of glucose transport in skeletal muscle isolated from db/db mice and L6 skeletal muscle cells. Oral glucose tolerance test was performed on db/db mice treated with CGA and soleus muscle was isolated for 2-deoxyglucose transport study. 2DG transport was also examined in L6 myotubes with or without inhibitors such as wortmannin or compound c. AMPK was knocked down with AMPKα1/2 siRNA to study its effect on CGA-stimulated glucose transport. GLUT 4 translocation, phosphorylation of AMPK and Akt, AMPK activity, and association of IRS-1 and PI3K were investigated in the presence of CGA. In db/db mice, a significant decrease in fasting blood sugar was observed 10 minutes after the intraperitoneal administration of 250 mg/kg CGA and the effect persisted for another 30 minutes after the glucose challenge. Besides, CGA stimulated and enhanced both basal and insulin-mediated 2DG transports in soleus muscle. In L6 myotubes, CGA caused a dose- and time-dependent increase in glucose transport. Compound c and AMPKα1/2 siRNA abrogated the CGA-stimulated glucose transport. Consistent with these results, CGA was found to phosphorylate AMPK and ACC, consistent with the result of increased AMPK activities. CGA did not appear to enhance association of IRS-1 with p85. However, we observed activation of Akt by CGA. These parallel activations in turn increased translocation of GLUT 4 to plasma membrane. At 2 mmol/l, CGA did not cause any significant changes in viability or proliferation of L6 myotubes. Our data demonstrated for the first time that CGA stimulates glucose transport in skeletal muscle via the activation of AMPK. It appears that CGA may contribute to the beneficial effects of coffee on Type 2 diabetes mellitus

Detecting pre-death grief in family caregivers of persons with dementia: measurement equivalence of the Mandarin-Chinese version of Marwit-Meuser caregiver grief inventory

Abstract Background Pre-death grief (PDG) is a key challenge faced by caregivers of persons with dementia (PWD). Marwit-Meuser Caregiver Grief Inventory (MM-CGI) and its abbreviated MM-CGI-Short-Form (MM-CGI-SF) are among the few empirically-developed scales that detect PDG. However, they have not had a Mandarin-Chinese version even though Chinese-speaking populations have among the largest number of PWD. We produced a Mandarin-Chinese version of MM-CGI and evaluated whether it had equivalent scores and similar psychometric properties to the English version. Methods We produced the Chinese MM-CGI through the methods of forward-backward translation and cognitive debriefing. Then, we recruited family caregivers of PWD (n = 394) to complete either the Chinese (n = 103) or English (n = 291) version. The two versions were compared in their score-difference (adjusting for potential confounders using multiple linear regression), internal-consistency reliability (using Cronbach’s α) and test-retest reliability (using intraclass correlation-coefficient), known-group validity (based on the relationship with the PWD and stage of dementia) and construct validity (using Spearman’s correlation-coefficient). Results The two versions showed similar mean scores, with the adjusted score-difference of 1.2 (90% CI -5.6 to 7.9) for MM-CGI and − 0.4 (90% CI -2.9 to 2.1) for MM-CGI-SF. The 90% CI for adjusted score-difference fell within predefined equivalence-margin (±8 for MM-CGI and ± 3 for MM-CGI-SF) and indicated equivalence of the scores. The two versions also demonstrated similar characteristics in reliability and validity. Conclusions The Chinese MM-CGI opens the way for PDG assessment and intervention among Chinese-speaking caregivers. Establishing its measurement equivalence with the English version paves the way for cross-cultural research on PDG in dementia caregiving