Kaji Noriyuki, Namekawa Junichi, Takagi Yoshiichi, Watanabe Ayaka, Nemoto Sayaka, Minami Yukako, Katayanagi Atusko, Kobayashi Taiki, Asai Fumitoshi
Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Azabu University, Sagamihara, Japan.
TEIJIN Pharma Limited, Hino, Japan.
Clin Exp Pharmacol Physiol. 2022 May;49(5):577-585. doi: 10.1111/1440-1681.13629. Epub 2022 Feb 22.
Fructose is considered to negatively affect type 2 diabetes mellitus (T2DM); however, there are contradictory reports. The present study aimed to elucidate the effects of fructose-rich diet (FRD) on glucose metabolism of Wistar Bonn Kobori (WBN/Kob) fatty diabetic (WBKDF) rats, a spontaneous T2DM model, and Wistar rats. Wistar Bonn Kobori fatty diabetic and Wistar rats were fed either FRD or standard diet (STD) for 4 weeks. The food intake, body weight, plasma glucose and insulin were measured weekly. After the 4-week challenge, rats were subjected to an intravenous glucose tolerance test (IVGTT). The liver and pancreas were used for histological analysis. The 4-week challenge of FRD in Wistar rats did not cause hyperglycaemia, but increased insulin resistance (Homeostatic Model Assessment for Insulin Resistance [HOMA-IR]). Feeding WBKDF rats with a FRD accelerated obesity, but prevented the onset of severe hyperglycaemia via maintaining high plasma insulin levels. Homeostatic Model Assessment for Insulin Resistance in WBKDF rats was not changed by FRD feeding. Intravenous glucose tolerance test revealed that FRD feeding in Wistar rats did not affect glucose tolerance, but slightly increased the plasma insulin level. In contrast, FRD feeding in WBKDF rats significantly reduced the glucose tolerance, but insulin response was not improved. Fructose-rich diet feeding did not alter the β cell area in Wistar rats, but significantly increased it in WBKDF rats. In conclusion, FRD caused insulin resistance in Wistar rats, suggesting that fructose overconsumption is a risk factor for T2DM, whereas FRD inhibited severe hyperglycaemia by maintaining high insulin levels in WBKDF rats. Fructose may be a beneficial sugar for T2DM patients with severe obesity-induced insulin resistance.
果糖被认为会对2型糖尿病（T2DM）产生负面影响；然而，也有相互矛盾的报道。本研究旨在阐明富含果糖的饮食（FRD）对Wistar Bonn Kobori（WBN/Kob）肥胖糖尿病（WBKDF）大鼠（一种自发性T2DM模型）和Wistar大鼠葡萄糖代谢的影响。将Wistar Bonn Kobori肥胖糖尿病大鼠和Wistar大鼠分别喂食FRD或标准饮食（STD）4周。每周测量食物摄入量、体重、血浆葡萄糖和胰岛素水平。在为期4周的实验期结束后，对大鼠进行静脉葡萄糖耐量试验（IVGTT）。取肝脏和胰腺进行组织学分析。对Wistar大鼠进行为期4周的FRD喂食并未导致高血糖，但增加了胰岛素抵抗（胰岛素抵抗稳态模型评估[HOMA-IR]）。给WBKDF大鼠喂食FRD会加速肥胖，但通过维持高血浆胰岛素水平可防止严重高血糖的发生。FRD喂养对WBKDF大鼠的胰岛素抵抗稳态模型评估没有影响。静脉葡萄糖耐量试验表明，给Wistar大鼠喂食FRD不影响葡萄糖耐量，但会使血浆胰岛素水平略有升高。相比之下，给WBKDF大鼠喂食FRD会显著降低葡萄糖耐量，但胰岛素反应并未改善。富含果糖的饮食喂养并未改变Wistar大鼠的β细胞面积，但在WBKDF大鼠中显著增加。总之，FRD在Wistar大鼠中引起胰岛素抵抗，表明果糖摄入过量是T2DM的一个风险因素，而FRD通过维持WBKDF大鼠的高胰岛素水平抑制了严重高血糖。果糖可能是患有严重肥胖诱导胰岛素抵抗的T2DM患者的一种有益糖类。
