PMID- 35749713 OWN - NLM STAT- MEDLINE DCOM- 20231023 LR - 20240412 IS - 1532-2378 (Electronic) IS - 1049-5398 (Linking) VI - 34 IP - 7 DP - 2023 Dec TI - Establishment of type 2 diabetes mellitus models using streptozotocin after 3 months high-fat diet in Bama minipigs. PG - 2295-2312 LID - 10.1080/10495398.2022.2088548 [doi] AB - In the past twenty years, the number of adults with diabetes has tripled. Most studies have been conducted using rodent models of type 2 diabetes mellitus (T2DM), and the developed drugs have low clinical conversion efficiency. Therefore, it is urgent to establish a more human-like large animal model to explore T2DM pathogenesis and formulate new disease prevention and control strategies. This study was designed to establish and validate a T2DM model using minipigs fed a high-fat or high-cholesterol/high-fat diet and injected with low-dose streptozotocin (STZ). We examined the influence of the STZ injection timing with a diet high in fat (HFD) compared with one high in cholesterol and fat (HCFD) on the atherosclerotic lesions accelerated by T2DM. Male Bama minipigs (n = 24) were randomly divided into five groups. The control group was fed a normal diet for 9 months. The STZ + HFD and STZ + HCFD groups were infused with 90 mg/kg STZ and then fed a high-fat diet or high-cholesterol and high-fat diet for 9 months, respectively. The HFD + STZ and HCFD + STZ groups were fed a high-fat diet or a high-cholesterol and high-fat diet, respectively, for 9 months (after 3 months, these pigs were injected intravenously with 90 mg/kg STZ). During the induction period, animal body weight, BMI, and serum GLU, INS, TG, TC, HDL-C, LDL-C, FFA, ALT, AST, CRE, and BUN were detected monthly intervals. IVGTT and insulin release tests were performed at 3-month intervals. At the end of the test, the coronary artery and abdominal aorta were examined by computed tomography and pathological observations, and the thickness of the basement membrane of the capillary of the retina and kidney glomerulus was measured under a transmission electron microscope. The serum glucose concentrations were normal in all groups except the HFD + STZ and HCFD + STZ groups. Animals fed an HFD for 9 months did not develop apparent atherosclerotic lesions, but atherosclerotic lesions were seen in the animals fed an HCFD. Hyperglycemia accelerated the formation of atherosclerotic lesions on the intimal surface of the abdominal aorta. Low-dose STZ after 3 months of HFD or HCFD successfully established a T2DM model in minipigs. The HFD did not induce apparent atherosclerotic lesions, but these were seen with the HCFD. Hyperglycemia accelerated atherosclerosis in the minipigs. FAU - Zhao, Yuqiong AU - Zhao Y AD - Laboratory Animal Center, Chinese PLA General Hospital, Beijing, China. FAU - Niu, Miaomiao AU - Niu M AD - Laboratory Animal Center, Chinese PLA General Hospital, Beijing, China. FAU - Jia, Yunxiao AU - Jia Y AD - Laboratory Animal Center, Chinese PLA General Hospital, Beijing, China. FAU - Yuan, Jifang AU - Yuan J AD - Laboratory Animal Center, Chinese PLA General Hospital, Beijing, China. FAU - Xiang, Lei AU - Xiang L AD - Laboratory Animal Center, Chinese PLA General Hospital, Beijing, China. FAU - Dai, Xin AU - Dai X AD - Laboratory Animal Center, Chinese PLA General Hospital, Beijing, China. FAU - Wang, Guisheng AU - Wang G AD - Radiology Department of No. 3 Clinical Center, Chinese PLA General Hospital, Beijing, China. FAU - Chen, Hua AU - Chen H AD - Laboratory Animal Center, Chinese PLA General Hospital, Beijing, China. LA - eng PT - Journal Article PT - Randomized Controlled Trial, Veterinary DEP - 20220624 PL - England TA - Anim Biotechnol JT - Animal biotechnology JID - 9011409 RN - 0 (Blood Glucose) RN - 97C5T2UQ7J (Cholesterol) RN - 5W494URQ81 (Streptozocin) SB - IM MH - Animals MH - Male MH - *Atherosclerosis MH - Blood Glucose MH - Cholesterol MH - *Diabetes Mellitus, Experimental/chemically induced MH - *Diabetes Mellitus, Type 2/etiology MH - Diet, High-Fat/adverse effects MH - Glucose Tolerance Test MH - *Hyperglycemia/complications MH - Streptozocin MH - Swine MH - Swine, Miniature OTO - NOTNLM OT - Type 2 diabetes OT - atherosclerosis OT - beta cell activity OT - miniature swine OT - streptozotocin EDAT- 2022/06/25 06:00 MHDA- 2023/10/23 12:44 CRDT- 2022/06/24 16:52 PHST- 2023/10/23 12:44 [medline] PHST- 2022/06/25 06:00 [pubmed] PHST- 2022/06/24 16:52 [entrez] AID - 10.1080/10495398.2022.2088548 [doi] PST - ppublish SO - Anim Biotechnol. 2023 Dec;34(7):2295-2312. doi: 10.1080/10495398.2022.2088548. Epub 2022 Jun 24.