Walnut-Derived Peptides Promote Autophagy via the Activation of AMPK/mTOR/ULK1 Pathway to Ameliorate Hyperglycemia in Type 2 Diabetic Mice

Abstract

Autophagy flux plays a significant protective role in type 2 diabetes mellitus (T2DM). However, the mechanisms by which autophagy mediates insulin resistance (IR) to ameliorate T2DM remain unclear. This study explored the hypoglycemic effects and mechanisms of walnut-derived peptides (fraction 3−10 kDa and LP5) in streptozotocin and high-fat-diet-induced T2DM mice. Findings revealed that walnut-derived peptides reduced the levels of blood glucose and FINS and ameliorated IR and dyslipidemia. They also increased SOD and GSH-P X activities and inhibited the secretion of TNF-α, IL-6, and IL-1β. Additionally, they increased the levels of ATP, COX, SDH, and MMP of liver mitochondria. Western blotting indicated that walnut-derived peptides upregulated LC3-II/LC3-I and Beclin-1 expression, while they down-regulated p62 expression, which may be associated with the activation of the AMPK/mTOR/ULK1 pathway. Finally, the AMPK activator (AICAR) and inhibitor (Compound C) were used to verify that LP5 could activate autophagy through the AMPK/mTOR/ULK1 pathway in IR HepG2 cells.

Therapeutic effects of a walnut-derived peptide on NLRP3 inflammasome activation, synaptic plasticity, and cognitive dysfunction in T2DM mice

“…To establish a mouse model of T2DM, we utilised the method outlined by Hou et al with minor adjustments. 21 During the study period, mice in the control group received a normal diet, whereas those in the T2DM group received a high-fat diet (HFD) to induce insulin resistance. Five weeks later, mice in the control group were administered an intraperitoneal injection of sodium citrate buffer ( pH 4.5) in accordance with their respective body weights (BW).…”

“…Similarly, Hou et al have demonstrated that walnut-derived peptides could improve insulin resistance and thus ameliorate glucose and lipid abnormalities and restore BW in diabetic mice. 21 Sun et al have reported that cereal peptides can attenuate insulitis and increase islet β-cell area to improve blood glucose levels in diabetic mice. 32 Taken together, we hypothesise that the TW-7 peptide could ameliorate insulin resistance in mice by increasing pancreatic β-cell sensitivity and enhancing lipid metabolism, thereby alleviating abnormal blood glucose and lipid levels.…”

Walnut-Derived Peptide Improves Cognitive Impairment in Colitis Mice Induced by Dextran Sodium Sulfate via the Microbiota–Gut–Brain Axis (MGBA)

“…The SSZ group mice were given 200 mg/kg bw of SSZ. The LP-5 group mice were given 60 mg/kg bw of LP-5 . For the treatment of colon inflammation, SSZ has been identified as an effective therapy.…”

“…The LP-5 group mice were given 60 mg/kg bw of LP-5. 18 For the treatment of colon inflammation, SSZ has been identified as an effective therapy. Mice were weighed daily throughout the DSS intervention, and their disease activity index (DAI) values were assessed using the previously suggested standards.…”

“…Over the past few years, research on walnut-derived peptides has gained significant momentum for their broad range of pharmacological activities, including the amelioration of cognitive deficits, antioxidative effects, antidiabetic effects, anti-inflammation effects, and immunomodulatory effects . Recently, the walnut protein-derived peptide LPF has been shown to suppress the secretion of proinflammatory factors and regulate gut dysbiosis in colitis mice .…”