| Objective: The prevalence of type-2 diabetes mellitus has been increasing in our country and even entire world along with social development and changing lifestyle. Malignant tumor threaten human healthy. Chemotherapy is one of main therapy to cure tumor. Along with the extending of a lot of tumor patients lives, more and more investigations were done to prevent the side effect of antitumor drugs. Many researchers have demonstrated that there are more and more new diabetes mellitus during or after chemotherapy. They pointed that the damage of islet cell by antitumor drugs may induce the direct impairment of glucose tolerance or diabetes mellitus. Mitomy- cin (MMC) is one of antitumor drugs commonly used and is used for many kinds of tumorous chemotherapy. Chemotherapy is combination of many antitumor drugs and multi-cycle. Tumor patients eat hyperalimentation and high fat diet during chemo- therapy intermission. But hyperalimentation and high fat diet reduces the insulin secretion and sensitivity. This is the lipo-toxicity theory of type-2 diabetes mellitus.In this research, rats were given the high fat diet and intra- venous injection with MMC, the effects of high fat diet and MMC on glucose tolerance and insulin secretion were examined.Methods: Forty-five healthy male Wistar rats (body weight 140±14g, age 6 weeks), were provided by Hebei Provincial Experimental Animal Center. The animals were randomly divid- ed into 3 groups: normal control, group HFD (high fat diet), and group HFD +MMC (high fat diet and MMC).Normal control received standard laboratory chow diet. Group HFD and group HFD +MMC were fed with high fat diet (65% fat, 25% carbohydrates and 10% protein). One rat in each cage, tempe- rature (20±3)℃, dampness 55%, lightness 12/24 hours.Rats were weighed at the beginning, before intravenous injec- tion and before the intraperitoneal glucose tolerance test (IP GTT). On the 6th day, MMC were adminisiered via intravenous injection at 1.67mg/kg in group HFD+MMC. Normal control and group HFD were injected saline (1.67mg/kg). The rats were fasted for 10 hours before IPGTT, and the blood samples were taken from tail vein. At the end of experiment, the blood samples were taken from femoral vein. Serum was stored at–20℃until used.1 Measurements of plasma glucose and insulin concentrations Glucose oxidation method was used for the determination of plasma glucose concentration and radioimmunoassay for the determination of plasma insulin concentration. Homeostasis Model Assessment (HOMA-IR) and insulin sensitivity index (ISI) were calculated to evaluate the resistance and sensitivity of insulin, ISI = 1/ (FINS×FPG), they were expressed by logari- thm.2 IPGTTThe rats in each group were subjected to the intraperitoneal glucose tolerance test (IPGTT). After 10h fast, the rats were intraperitoneally injection with glucose at 2.0mg/kg. The blood samples were taken from the vena caudalis before (0 minute) and 30, 60 and 120 minutes after glucose loading. Plasma glucose concentrations were determined immediately, and the remaining sera were stored at -20℃for the measurement of plasma insulin concentrations.3 Blood lipidTotal cholesterol (TCHO), triglyceride (TG) and high density lipoprotein-cholesterol (HDL-C) were measured by chronometry. FFAs were measured by the ratio of Cu2+ chrom.Results:1 Results of weightThere were no significant difference in weight among each group at the beginning of the experiment, before intravenous injection and before the intraperitoneal glucose tolerance test (P>0.05).2 Results of IPGTTThe fasting plasma glucose (FPG) and the plasma glucose concentrations at 30min, 60min and 120min after glucose load- ing in group HFD, and group HFD+MMC were higher than those in normal control (P<0.05). The plasma glucose concentrations at 30min, 60min and 120min in group HFD +MMC were higher than those in group HFD (P <0.05).3 Results of plasma glucose-stimulated insulin secretionThe fasting plasma insulin concentrations in group HFD +MMC were lower than those in normal control (P <0.05). The fasting plasma insulin concentrations in group HFD+MMC were lower than those in group HFD (P<0.05). There were no significant difference in fasting plasma insulin concentrations between group HFD and normal control (P>0.05). The 20-min postload insulin concentrations in group HFD+MMC and group HFD were lower than those in normal control (P<0.05). The 20-min postload insulin concentrations in group HFD+MMC were lower than those in group HFD (P<0.05). The 60-min and 120-min postload insulin concentrations in group HFD+MMC were lower than those in normal control (P< 0.05). The 60-min and 120-min postload insulin concentrations in group HFD+ MMC were lower than those in group HFD (P<0.05). There were no significant difference in 60-min and 120-min postload insulin concentrations between group HFD and normal control (P>0.05).4 HOMA-IR and ISIThere were no significant difference in HOMA-IR or ISI between group HFD and group HFD+MMC (P>0.05). HOMA- IR in group HFD and group HFD+MMC were higher than those in normal control (P<0.05). ISI in group HFD and group HFD+ MMC were lower than those in normal control (P<0.05).5 Blood lipid and hepatic function At the end of experiment, there were no significant difference in ALT, AST, and GGT among each group (P>0.05). There were no significant difference in TCHO among each group (P>0.05). All concentrations of TG, LDL-C, and FFA in group HFD+ MMC and group HFD were higher than those in normal control (P<0.05). The concentrations of HDL-C in group HFD+MMC and group HFD were lower than those in normal control (P<0.05). There were no significant difference in all concentra- tions of TG, LDL-C, and FFA between group HFD+MMC and group HFD (P>0.05).Conclusions:1 High fat diet reduces insulin secretion and sensitivity.2 MMC inhibits insulin secretion.3 The glucose tolerance in rats is impaired by the function combination of high fat diet and MMC. |
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