Small Molecule Kaempferol Promotes Insulin Sensitivity and Preserved Pancreaticβ-Cell Mass in Middle-Aged Obese Diabetic Mice

Abstract

Insulin resistance and a progressive decline in functional β-cell mass are hallmarks of developing type 2 diabetes (T2D). Thus, searching for natural, low-cost compounds to target these two defects could be a promising strategy to prevent the pathogenesis of T2D. Here, we show that dietary intake of flavonol kaempferol (0.05% in the diet) significantly ameliorated hyperglycemia, hyperinsulinemia, and circulating lipid profile, which were associated with the improved peripheral insulin sensitivity in middle-aged obese mice fed a high-fat (HF) diet. Kaempferol treatment reversed HF diet impaired glucose transport-4 (Glut4) and AMP-dependent protein kinase (AMPK) expression in both muscle and adipose tissues from obese mice. In vitro, kaempferol increased lipolysis and prevented high fatty acid-impaired glucose uptake, glycogen synthesis, AMPK activity, and Glut4 expression in skeletal muscle cells. Using another mouse model of T2D generated by HF diet feeding and low doses of streptozotocin injection, we found that kaempferol treatment significantly improved hyperglycemia, glucose tolerance, and blood insulin levels in obese diabetic mice, which are associated with the improved islet β-cell mass. These results demonstrate that kaempferol may be a naturally occurring anti-diabetic agent by improving peripheral insulin sensitivity and protecting against pancreatic β-cell dysfunction.

Bioactivity-guided isolation of antidiabetic principles from the methanolic leaf extract ofBryophyllum pinnatum

“…Comparison of the 1 H and 13 C NMR data for fractions A and B revealed that these compounds are quercetin and kaempferol, respectively (Figure ) (Ibrahim, Amin, Ibrahim, Abdelzaher, & Abdelrahman, ). Interestingly, previous studies have demonstrated the antidiabetic activity of quercetin (Abdelkarem & Fadda, ; Srinivasan, Vijayakumar, Kothandaraman, & Palani, ; Yang & Kang, ) and kaempferol (Alkhalidy et al, ; Chandramohan, Al‐Numair, Alsaif, & Veeramani, ; Zang, Zhang, Igarashi, & Yu, ) in different models. The reduction in blood glucose shows that these compounds contribute to the blood glucose lowering activity of methanolic leaf extract of B. pinnatum .…”

“…Depending on the prevalence and sophistication of treatment, a 2.5%–15% annual health budget costs have been directly linked to the menace caused by diabetes (American Diabetes Association, ). Although the aetiology of this disease is not well characterized, there are indications of associated pancreatic β‐cells dysfunction (Alkhalidy et al, ). In addition to the elevated blood glucose, complications such as chronic inflammation, oxidative stress, lipotoxicity, endoplasmic reticulum (ER) stress (Ozcan et al, ; Poitout & Robertson, ) retinopathy (Hove, Kristensen, Lauritzen, & Bek, ), neuropathy (Moran et al, ), nephropathy (Huang et al, ), cardiovascular complications (Saely, Aczel, Marte, Langer, & Drexel, ) and ulcerations (Wallace et al, ) are well documented in diabetes.…”

The protective effect of kaempferol on heart via the regulation of Nrf2, NF‐κβ, and PI3K/Akt/GSK‐3β signaling pathways in isoproterenol‐induced heart failure in diabetic rats

“…The STZ treatment results in insufficient production of insulin and thereby leads to elevated blood glucose levels (Giribabu, Kumar, Rekha, Muniandy, & Salleh, ). A previous study demonstrated that KF could decrease the blood glucose levels due to improved peripheral insulin sensitivity (Alkhalidy et al, ). Recently, it was also demonstrated that KF controls the blood glucose levels via promoting glucose metabolism in skeletal muscle and inhibiting gluconeogenesis in the liver (Alkhalidy et al, ).…”

“…The STZ treatment results in insufficient production of insulin and thereby leads to elevated blood glucose levels (Giribabu, Kumar, Rekha, Muniandy, & Salleh, 2014). A previous study demonstrated that KF could decrease the blood glucose levels due to improved peripheral insulin sensitivity (Alkhalidy et al, 2015).…”

Brazilian Green Propolis Promotes Weight Loss and Reduces Fat Accumulation in C57BL/6 Mice Fed A High-Fat Diet

“…19,20) Intake of kaempferol ameliorates hyperglycemia, hyperinsulinemia and circulating lipid profile, which are associated with improved peripheral insulin sensitivity in mice fed a high-fat diet. 21,22) Upregulation of carnitine palmitoyltransferase 1 by p-coumaric acid improves liver fat metabolism. 23) Further studies are needed to clarify what components are effective for weight control.…”