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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 G\u00f6ttingen Minipigs.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Bitter gourd fruit from the cultivars \u201cPalee\u201d and \u201cGood healthy\u201d reduced plasma fructosamine concentrations in all pigs combined (from 450\u00b148 to 423\u00b153 and 490\u00b150 to 404\u00b148 \u03bcmol\/L, both p&lt;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 \u201cPalee\u201d (&gt;3.9-fold) and \u201cGood healthy\u201d (&gt;8.9-fold) compared to the mean of the other three cultivars. Bitter gourd stems and leaves from the cultivar \u201cBilai\u201d increased plasma insulin concentrations in all pigs combined by 28% (from 53\u00b16 to 67\u00b19 pmol\/L, p&lt;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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0298163","type":"journal-article","created":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T17:42:09Z","timestamp":1710783729000},"page":"e0298163","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Momordica charantia fruit reduces plasma fructosamine whereas stems and leaves increase plasma insulin in adult mildly diabetic obese G\u00f6ttingen Minipigs"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8238-4770","authenticated-orcid":true,"given":"Sietse 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