Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Physiology, Faculty of Animal and Veterinary Sciences, Shabestar Branch, Islamic Azad University, Shabestar, Iran.
J Diabetes Investig. 2019 Sep;10(5):1177-1188. doi: 10.1111/jdi.13018. Epub 2019 Mar 12.
AIMS/INTRODUCTION: Peptides are considered to be quasi-hormones and effective molecules for regulation of the cells function and prevention of metabolic disorders. Di- and tripeptides gastrointestinal absorption ability have been proposed to prevent diabetes progression.
Small peptides with different sequences of specific amino acids were synthesized based on a solid phase peptide synthesis protocol, and carnosine (A) and glutathione were examined for the prevention of diabetes induced by multiple low-doses of streptozotocin in mice.
The peptides A, Leu-Gly (D) and Pro-Pro showed preventive effects on blood glucose elevation and impairment of the signaling and performance of β-cells. The β-cell function assessed by immunofluorescence and blood glucose level in mice exposed to diabetes treated by the peptides A and D was similar to the normal mice. The peptide D prevented bodyweight loss caused by diabetes induction. The use of D and A peptides dramatically prevented the incidence of disruption in β-cells signaling by maintaining the natural balance of intracellular Akt-2 and cyclic adenosine monophosphate.
The results proved that peptide D (Leu-Gly), named Hannaneh, inhibits the bodyweight loss caused by diabetes induction. The Hannaneh and carnosine dipeptides, with preservation of normal β-cell signaling and anti dipeptidyl peptidase-4 activity, prevented blood glucose increases in mice at risk of diabetes. These dipeptides might be regarded as the pharmaceutical agents for the prevention of diabetes.
目的/引言：肽被认为是准激素和有效的细胞功能调节分子，可预防代谢紊乱。二肽和三肽的胃肠道吸收能力被认为可预防糖尿病的进展。
根据固相肽合成方案合成了具有特定氨基酸不同序列的小肽，并研究了肌肽（A）和谷胱甘肽对预防小鼠多次低剂量链脲佐菌素诱导的糖尿病的作用。
肽 A、亮氨酰甘氨酸（D）和脯氨酰脯氨酸显示出预防血糖升高和β细胞信号转导及功能障碍的作用。用肽 A 和 D 治疗的暴露于糖尿病的小鼠的β细胞功能通过免疫荧光和血糖水平进行评估，与正常小鼠相似。肽 D 可预防糖尿病诱导引起的体重减轻。使用 D 和 A 肽可通过维持细胞内 Akt-2 和环腺苷单磷酸的自然平衡来显著防止β细胞信号转导的破坏，从而显著降低二肽基肽酶-4的活性。
结果证明肽 D（亮氨酰甘氨酸），命名为 Hannaneh，可抑制糖尿病诱导引起的体重减轻。Hannaneh 和肌肽二肽通过维持正常的β细胞信号转导和抗二肽基肽酶-4活性，可预防糖尿病风险小鼠的血糖升高。这些二肽可能被视为预防糖尿病的药物。
