J Agric Food Chem:喝咖啡能降低2型糖尿病發病風險嗎?

2型糖尿病的全球發病人數越來越多，導致越來越嚴重的健康問題。為什麼經常喝喝咖啡的人患2型糖尿病的風險比較低？科學家們最近在ACS的J Agric Food Chem雜誌上發表的一篇報導"Coffee Components Inhibit Amyloid Formation of Human Islet Amyloid Polypeptide in Vitro: Possible Link between Coffee Consumption and Diabetes Mellitus"對這個長期未解之謎提供了一個新答案。

Ling Zheng，Kun Huang和同事們解釋說：之前的研究顯示喝咖啡的人患2型糖尿病的風險比較低，而全球範圍內，2型糖尿病患者佔總的糖尿病患者的90%到95%。那些研究顯示每天喝4杯咖啡或更多的人患2型糖尿病的風險降低50%。在此基礎上，每多喝一杯咖啡，患病風險降低7%。科學家已經暗示一種稱為人胰島類澱粉多肽（hIAPP）的錯誤摺疊會引起2型糖尿病；而且科學家正在尋找阻斷該蛋白錯誤摺疊的過程。Zheng和Huang決定驗證一下咖啡降低2型糖尿病的患病風險是不是來源於咖啡中含有某種可以阻斷hIAPP錯誤摺疊的物質。

他們確實在咖啡中發現了兩類化合物，這些化合物可以顯著抑制hIAPP的錯誤摺疊過程。他們提出正是由於這種作用解釋了為什么喝咖啡的人患糖尿病的風險比較低。研究者們總結說：「因此，經常喝咖啡的人會得到預期的有益效果（患2型糖尿病的風險降低）。」

作者感謝中國國家自然科學基金、中國國家基礎研究項目和中國教育部的基金支持。（生物谷Bioon.com）

Coffee Components Inhibit Amyloid Formation of Human Islet Amyloid Polypeptide in Vitro: Possible Link between Coffee Consumption and Diabetes Mellitus

Biao Cheng†, Xinran Liu†, Hao Gong†, Lianqi Huang†, Hong Chen†, Xin Zhang†, Chuanzhou Li§, Muyang Yang†, Bingjun Ma†, Lihua Jiao†, Ling Zheng*§, and Kun Huang*†#

Global epidemic studies have suggested that coffee consumption is reversely correlated with the incidence of type 2 diabetes mellitus (T2DM), a metabolic disease. The misfolding of human islet amyloid polypeptide (hIAPP) is regarded as one of the causative factors of T2DM. Coffee extracts have three major active components: caffeine, caffeic acid (CA), and chlorogenic acid (CGA). In this study, the effects of these major coffee components, as well as dihydrocaffeic acid (DHCA) (a major metabolite of CGA and CA), on the amyloidogenicity of hIAPP were investigated by thioflavin-T based fluorescence emission, transmission electronic microscopy, circular dichroism, light-induced cross-linking, dynamic light scattering, and MTT-based cell viability assays. The results suggest that all components show varied inhibitory effects on the formation of toxic hIAPP amyloids, in which CA shows the highest potency in delaying the conformational transition of the hIAPP molecule with the most prolonged lag time, whereas caffeine shows the lowest potency. At a 5-fold excess molar ratio of compound to hIAPP, all coffee-derived compounds affect the secondary structures of incubated hIAPP as suggested by the circular dichroism spectra and CDPro deconvolution analysis. Further photoinduced cross-linking based oligomerization and dynamic light scattering studies suggested CA and CGA significantly suppressed the formation of hIAPP oligomers, whereas caffeine showed no significant effect on oligomerization. Cell protection effects were also observed for all three compounds, with the protection efficiency being greatest for CA and least for CGA. These findings suggest that the beneficial effects of coffee consumption on T2DM may be partly due to the ability of the major coffee components and metabolites to inhibit the toxic aggregation of hIAPP.