Key result
STZ-induced diabetes markedly increases plasma triglycerides in LDLR-deficient hamsters, reversed by insulin.
Why the study?
Inducing diabetic hypertriglyceridemia typically requires high-fat diets in animal models, so researchers tested whether LDL receptor knockout hamsters develop hypertriglyceridemia without dietary manipulations in diabetes.
Does streptozotocin-induced diabetes cause spontaneous insulin-dependent hypertriglyceridemia without high-fat dietary manipulation in heterozygous LDL receptor-deficient hamsters?
Does streptozotocin-induced diabetes cause spontaneous insulin-dependent hypertriglyceridemia without high-fat dietary manipulation in heterozygous LDL receptor-deficient hamsters?
This study establishes a novel preclinical model of spontaneous, insulin-dependent severe hypertriglyceridemia in diabetic heterozygous LDLR-deficient hamsters on a normal chow diet, offering a human-like model to study diabetic dyslipidemia and its vascular complications.
Answers are grounded in this paper and cite their sources.
Establishes a novel chow-fed hamster model of insulin-reversible diabetic hypertriglyceridemia; leaves open translation to human disease.
Hypertriglyceridemia (HTG) often accompanies diabetes and is considered a risk factor for diabetic vascular complications. However, inducing diabetic HTG typically requires high-fat diets in certain animal models. Leveraging our newly developed LDL receptor knockout hamster model, which exhibits features akin to human lipid metabolism, we sought to determine whether these animals would develop HTG without dietary manipulations in diabetes. Diabetes was induced via intraperitoneal injection of STZ in wild type and heterozygous LDL receptor deficient hamsters. Blood glucose, triglyceride, and cholesterol were measured over 60 days. Plasma TG clearance was determined via olive oil gavage. The effect of insulin on diabetic HTG was assessed on Day 60 post-diabetes induction. Blood glucose increased over threefold, while plasma insulin decreased to 30% of controls after STZ injection in both wild type and heterozygous hamsters by Day 7, remaining stable for 60 days. Plasma TG in wild-type hamsters remained unchanged at Day 7 post-STZ injection but increased slightly thereafter. Conversely, heterozygous hamsters exhibited severe HTG by Day 7 until the end of the study. Olive oil gavage revealed much slower plasma triglyceride clearance in heterozygous hamsters compared to WT animals, despite significantly reduced lipoprotein lipase activity in post-heparin plasma in both animals. Hyperglycemia and HTG in heterozygous hamsters were reversed to pre-diabetic levels following intraperitoneal insulin administration. In conclusion, severe HTG in diabetic heterozygous LDL receptor deficient hamsters developed spontaneously and was insulin-dependent. Thus, this hamster model holds promise for effectively studying the complications associated with human diabetic HTG.
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Ma et al. (2024) studied Diabetic hypertriglyceridemia in LDLR-deficient hamsters (n=33). Streptozotocin (STZ) diabetes induction followed by insulin rescue vs. Non-diabetic control wild-type and heterozygous LDLR-deficient hamsters was evaluated on Plasma triglyceride concentration at Day 7 post-STZ injection in heterozygous LDLR-deficient hamsters (mg/dL) (p=<0.01). Streptozotocin-induced diabetes increased plasma triglycerides nearly 7-fold by Day 7 in heterozygous LDLR-deficient hamsters on chow diet (726 vs 126 mg/dL, p<0.01), which was reversed by insulin.
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