Division of Diabetes, Endocrinology and Metabolism, Section of Endocrinology and Investigative Medicine, Imperial College London, London, UK.
Research Department, Imperial College London Diabetes Centre, Abu Dhabi, United Arab Emirates.
Diabetes Metab Res Rev. 2024 Jul;40(5):e3829. doi: 10.1002/dmrr.3829.
Pancreatic polypeptide (PP) is elevated in people with vascular risk factors such as type 2 diabetes or increased visceral fat. We investigated potential relationships between PP and microvascular and macrovascular complications of diabetes.
Animal study: Subcutaneous PP infusion for 4 weeks in high fat diet mouse model. Retinal mRNA submitted for Ingenuity Pathway Analysis. Human study: fasting PP measured in 1478 participants and vascular complications recorded over median 5.5 (IQR 4.9-5.8) years follow-up.
Animal study: The retinal transcriptional response to PP was indicative of cellular stress and damage, and this footprint matched responses described in previously published studies of retinal disease. Of mechanistic importance the transcriptional landscape was consistent with upregulation of folliculin, a recently identified susceptibility gene for diabetic retinopathy. Human study: Adjusting for established risk factors, PP was associated with prevalent and incident clinically significant retinopathy (odds ratio (OR) 1.289 (1.107-1.501) p = 0.001; hazard ratio (HR) 1.259 (1.035-1.531) p = 0.0213), albuminuria (OR 1.277 (1.124-1.454), p = 0.0002; HR 1.608 (1.208-2.141) p = 0.0011), and macrovascular disease (OR 1.021 (1.006-1.037) p = 0.0068; HR 1.324 (1.089-1.61), p = 0.0049), in individuals with type 2 diabetes, and progression to diabetes in non-diabetic individuals (HR 1.402 (1.081-1.818), p = 0.0109).
Elevated fasting PP is independently associated with vascular complications of diabetes and affects retinal pathways potentially influencing retinal neuronal survival. Our results suggest possible new roles for PP-fold peptides in the pathophysiology of diabetes complications and vascular risk stratification.
胰多肽（PP）在患有 2 型糖尿病或内脏脂肪增加等血管危险因素的人群中升高。我们研究了 PP 与糖尿病微血管和大血管并发症之间的潜在关系。
动物研究：在高脂肪饮食的小鼠模型中进行皮下 PP 输注 4 周。对视网膜 mRNA 进行 Ingenuity 通路分析。人类研究：在 1478 名参与者中测量空腹 PP，并在中位 5.5 年（四分位距 4.9-5.8）的随访中记录血管并发症。
动物研究：PP 对视网膜的转录反应表明存在细胞应激和损伤，这种反应与先前发表的视网膜疾病研究中描述的反应一致。具有机制重要性的是，转录谱与卵泡抑素的上调一致，卵泡抑素是最近发现的糖尿病性视网膜病变易感性基因。人类研究：调整了已确立的危险因素后，PP 与现患和新发临床显著视网膜病变（比值比（OR）1.289（1.107-1.501），p=0.001；风险比（HR）1.259（1.035-1.531），p=0.0213）、白蛋白尿（OR 1.277（1.124-1.454），p=0.0002；HR 1.608（1.208-2.141），p=0.0011）和大血管疾病（OR 1.021（1.006-1.037），p=0.0068；HR 1.324（1.089-1.61），p=0.0049）相关，在 2 型糖尿病患者中与大血管疾病相关，并且在非糖尿病患者中进展为糖尿病（HR 1.402（1.081-1.818），p=0.0109）。
空腹 PP 升高与糖尿病血管并发症独立相关，并影响视网膜通路，可能影响视网膜神经元的存活。我们的研究结果表明，PP 折叠肽在糖尿病并发症和血管风险分层的病理生理学中可能具有新的作用。
