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| Effect of Kaempferol on Apoptosis of Pancreatic Beta Cells in Streptozotocin-induced Diabetes Mellitus Rats via Regulating cAMP/PKA/CREB Signaling Pathway |
| MA Jianna, CAO Sangbo, LIU Kerou, et al |
| The Affiliated Hospital of Tangshan Vocational & Technical College, Hebei Tangshan 063000, China |
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Abstract Objective: To investigate the effect of kaempferol (Kae) on apoptosis of pancreatic beta cells (PBC) in streptozotocin (STZ)-induced diabetes mellitus (DM) rats via regulating cyclic adenosine monophosphate (cAMP) / protein kinase A (PKA) / cAMP-response element binding protein (CREB) signaling pathway. Methods: Sixty Sprague-Dawley (SD) rats were separated into control check (CK) group, model group, Kae low-dose group (Kae-L) group, Kae high-dose group (Kae-H) group, and Kae H+cAMP inhibitor (H-89) group, with 12 rats in each group. Blood glucose meter was used to detect fasting plasma glucose (FPG). Enzyme-linked immunosorbent assay (ELISA) was applied to detect the levels of serum fasting insulin (FINS) and interleukin-10 (IL-10), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and cAMP in pancreatic tissue. Reagent kits were applied to detect malondialdehyde (MDA) content, superoxide dismutase (SOD) and catalase (CAT) activities in pancreatic tissue. Hematoxylin-eosin (H&E) staining was applied to observe the morphology of pancreatic tissue. Aldehyde fuchsin orange yellow G staining was applied to assess the apoptosis of PBC. Western blot was applied to detect the expression of cleaved caspase-3, Bcl-2-associated x (Bax), B-cell lymphoma 2 (Bcl-2), PKA, and CREB proteins in pancreatic tissue. Results: Compared with the CK group, the model group rats had incomplete pancreatic islet cells, blurred boundaries between pancreatic islet cells and surrounding cells, and pancreatic islet atrophy, significantly decreased PDC number, increased FPG, FINS, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and IL-6 and TNF-α levels, MDA content, cleaved caspase-3 and Bax protein expression, reduced IL-10 and cAMP levels, SOD and CAT activities, and Bcl-2, p-PKA/PKA, and p-CREB/CREB proteins expression (P<0.05). Compared with the model group, rats in the Kae-L and Kae-H groups presented a obvious improvement in the morphology of pancreatic islet cells, significantly increased PBC number, decreased FPG, FINS, HOMA-IR, levels of IL-6 and TNF-α levels, MDA content, cleaved caspase-3 and Bax protein expression, elevated IL-10 and cAMP levels, SOD and CAT activities, and Bcl-2, p-PKA/PKA, and p-CREB/CREB proteins expression (P<0.05). H-89 could attenuate the effect of Kae on the apoptosis of PBC in DM rats (P<0.05). Conclusion: Kae can alleviate inflammation and oxidative stress, and reduce apoptosis of PBC via activating the cAMP/PKA/CREB signaling pathway.
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2025, Vol. 31 
