Contribution of hyperglycemia on diabetic complications in obese type 2 diabetic SDT fatty rats: effects of SGLT inhibitor phlorizin

Abstract

The spontaneously diabetic torii (SDT) fatty rat is a new model of type 2 diabetes showing overt obesity, hyperglycemia and hyperlipidemia. With early onset of diabetes mellitus, diabetic microvascular complications, including nephropathy, peripheral neuropathy and retinopathy, are observed at young ages. In the present study, blood glucose levels of female SDT fatty rats were controlled with phlorizin, a non-selective SGLT inhibitor, to examine whether and how these complications are caused by hyperglycemia. Phlorizin treatment adequately controlled plasma glucose levels during the experiment. At 29 weeks of age, urinary albumin excretion considerably increased in SDT fatty rats. Glomerulosclerosis and tubular pathological findings also indicate diabetic nephropathy. These renal parameters tended to decrease with phlorizin; however, effects were partial. Sciatic nerve conduction velocities were significantly delayed in SDT fatty rats compared with Sprague-Dawley (SD) rats. Intraepidermal nerve fiber density, an indicator of subclinical small nerve fiber neuropathy, significantly decreased in SDT fatty rats. Retinal dysfunction (prolongation of peak latency for oscillatory potential in electroretinograms) and histopathological eye abnormalities, including retinal folding and mature cataracts were also observed. Both nerve and eye disorders were prevented with phlorizin. These findings indicate that severe hyperglycemia mainly causes diabetic complications in SDT fatty rats. However, other factors, such as hyperlipidemia and hypertension, may affect diabetic nephropathy. These characteristics of diabetic complications will become helpful in evaluating new drugs for diabetic complications using SDT fatty rats.

Depression‐related behavioural and neuroendocrine changes in the Spontaneously Diabetic Torii (SDT) fatty rat, an animal model of type 2 diabetes mellitus

“…This variability in SDT fatty rats may result from differences in the development of hyperglycaemia. Indeed, although previous studies suggested that SDT fatty rats develop hyperglycaemia from a young age, the animals used in the present study showed a wide range of plasma glucose concentrations (Table ).…”

“…The Spontaneously Diabetic Torii (SDT) fatty rat is a novel animal model of type 2 DM that develops not only hyperglycaemia, but also hyperlipidaemia and insulin resistance from a young age . In the present study, we investigate whether SDT fatty rats show depression‐like behaviour using an FST.…”

“…The Spontaneously Diabetic Torii (SDT) fatty rat is a novel animal model of type 2 DM that develops not only hyperglycaemia, but also hyperlipidaemia and insulin resistance from a young age. 12 In the present study, we investigate whether SDT fatty rats show depression-like behaviour using an FST. The FST has frequently been used for the screening of antidepressants and assessment of depressive features in animal models of depression and transgenic or knockout rodents.…”

Apple phlorizin supplementation attenuates oxidative stress in hamsters fed a high-fat diet

“…This result was in agreement with the previous report which demonstrated that the levels of serum fasting blood glucose, TG, and TC in db/db mice increased as compared to the control group, while the oral administration of phlorizin reduced these levels significantly (Cai et al, ). According to a previous report, plasma TC and glucose levels were considerably decreased in 18‐week‐old female diabetic tori fatty rats when administered subcutaneously with 100 mg/kg phlorizin (Katsuda et al, ). Another study found that high‐fat diet increased the non‐HDL‐cholesterol and plasma free fatty acid levels in rats; however, these levels were lowered significantly in the phlorizin‐treated group (0.02%, w/w) (Shin, Cho, Jung, Ryu, & Choi, ).…”

Meta-Analysis And Meta-Regression Of The Prevalence Of Diabetic Peripheral Neuropathy Among Patients With Type 2 Diabetes Mellitus

“…More than half of all individuals with diabetes exhibit one or more microvascular complications, including diabetic nephropathy (DN), diabetic peripheral neuropathy (DPN), or diabetic retinopathy (DR), which have a serious negative impact on the quality of life of patients [5,6].…”