Ingredients of mild obesogenic diet.

Background
Traditionally Momordica charantia (Bitter gourd) is known for its blood glucose lowering potential. This has been validated by many previous studies based on rodent models but human trials are less convincing and the physiological mechanisms underlying the bioactivity of Bitter gourd are still unclear. The present study compared the effects of whole fruit or stems-leaves from five different Bitter gourd cultivars on metabolic control in adult diabetic obese Göttingen Minipigs.
Methods
Twenty streptozotocin-induced diabetic (D) obese Minipigs (body weight ~85 kg) were subdivided in mildly and overtly D pigs and fed 500 g of obesogenic diet per day for a period of three weeks, supplemented with 20 g dried powdered Bitter gourd or 20 g dried powdered grass as isoenergetic control in a cross-over, within-subject design.
Results
Bitter gourd fruit from the cultivars “Palee” and “Good healthy” reduced plasma fructosamine concentrations in all pigs combined (from 450±48 to 423±53 and 490±50 to 404±48 μmol/L, both p<0.03, respectively) indicating improved glycemic control by 6% and 17%. These effects were statistically confirmed in mildly D pigs but not in overtly D pigs. In mildly D pigs, the other three cultivars of fruit showed consistent numerical but no significant improvements in glycemic control. The composition of Bitter gourd fruit was studied by metabolomics profiling and analysis identified three metabolites from the class of triterpenoids (Xuedanoside H, Acutoside A, Karaviloside IX) that were increased in the cultivars “Palee” (>3.9-fold) and “Good healthy” (>8.9-fold) compared to the mean of the other three cultivars. Bitter gourd stems and leaves from the cultivar “Bilai” increased plasma insulin concentrations in all pigs combined by 28% (from 53±6 to 67±9 pmol/L, p<0.03). The other two cultivars of stems and leaves showed consistent numerical but no significant increases in plasma insulin concentrations. The effects on plasma insulin concentrations were confirmed in mildly D pigs but not in overtly D pigs.
Conclusions
Fruits of Bitter gourd improve glycemic control and stems-leaves of Bitter gourd increase plasma insulin concentrations in an obese pig model for mild diabetes. The effects of Bitter gourd fruit on glycemic control seem consistent but relatively small and cultivar specific which may explain the varying results of human trials reported in the literature.

背景
传统上，苦瓜（Momordica charantia，别名Bitter gourd）以其降血糖潜力为人熟知。此前多项基于啮齿类动物模型的研究已证实该功效，但人体试验结果却说服力不足，且苦瓜生物活性背后的生理机制仍未明确。本研究对比了5个不同苦瓜品种的全果或茎叶，对成年糖尿病肥胖哥廷根迷你猪（Göttingen Minipigs）代谢调控的效果。

方法
本研究选取20只链脲佐菌素（streptozotocin）诱导的糖尿病肥胖迷你猪（体重约85 kg），将其分为轻度糖尿病组与显性糖尿病组；每日饲喂500 g致肥胖饲料，为期3周，并采用受试者内交叉设计，额外添加20 g苦瓜干燥粉末或20 g干草干燥粉末作为等热量对照。

结果
“Palee”与“Good healthy”两个品种的苦瓜果实，可降低所有受试猪的血浆果糖胺浓度（分别从450±48 μmol/L降至423±53 μmol/L、490±50 μmol/L降至404±48 μmol/L，两者p值均<0.03），提示血糖调控能力分别提升6%与17%。该效果在轻度糖尿病猪中得到统计学验证，但在显性糖尿病猪中未观察到显著改善。在轻度糖尿病猪中，其余3个品种的苦瓜果实虽在数值上呈现一致趋势，但未使血糖调控得到显著提升。本研究通过代谢组学分析（metabolomics profiling）对苦瓜果实的成分进行了研究，鉴定出3种三萜类（triterpenoids）代谢物：雪胆苷H（Xuedanoside H）、尖叶苦瓜苷A（Acutoside A）、苦瓜苷IX（Karaviloside IX）；与其余3个品种的平均值相比，“Palee”与“Good healthy”品种中这3种代谢物的含量分别升高3.9倍以上与8.9倍以上。“Bilai”品种的苦瓜茎叶可使所有受试猪的血浆胰岛素浓度整体升高28%（从53±6 pmol/L升至67±9 pmol/L，p<0.03）。其余2个品种的苦瓜茎叶虽在数值上呈现一致的升高趋势，但未使血浆胰岛素浓度得到显著提升。该效果在轻度糖尿病猪中得到验证，但在显性糖尿病猪中未观察到显著改善。

结论
在轻度糖尿病肥胖迷你猪模型中，苦瓜果实可改善血糖调控，而苦瓜茎叶则可升高血浆胰岛素浓度。苦瓜果实对血糖调控的效果虽具有一致性，但幅度相对较小且存在品种特异性，这或许可解释此前文献中报道的人体试验结果存在差异的原因。