Effects Of Goat Milk On Glucose Metabolism And The Possible Mechanism

Objective To explore the effects of goat milk on glucose metabolism and the possible mechanism.Methods The study was divided into two parts.The first part was to explore the effects of goat milk on type 1 diabetes(T1D).180±20g male SD rats were intraperitoneally injected with 60 mg/kg streptozocin(STZ).The 48 diabetic rats,which were successfully modeled,were randomly divided into 6 groups(8 in each group): diabetes model group(deionized water),low-,medium-,and high-dose goat milk intervention groups(2.5,5,10g/kg goat milk power),cow milk intervention group(10g/kg cow milk power),and metformin group(0.2g/kg metformin).The normal rats were randomly divided into the control group(deionized water)and goat milk high-dose control group(10g/kg goat milk power).Gavage was administered daily for 30 days.Fasting blood glucose was measured on days 0,15 and 30.On day 22,the insulin resistance test(ITT)was conducted,and on day 28,the oral glucose tolerance test(OGTT)was conducted.On day 30,the rats were killed.The levels of CHO,TG,HDL,LDL,HbA1 c,adiponectin,insulin,GLP-1,PYY and TNF-? in serum were measured.The expression levels of AMPK,PEPCK,and G6 Pase in the liver,and the protein levels of AMPK,GLUT4 and hexokinase2 in the skeletal muscle,were detected by western blot.The colonic contents were collected to analyze the gut microbiota and short chain fatty acids.The second part was to explore the effects of goat milk on high fat diet(HFD)induced glucose metabolism disorder.72 male SD rats aged 4 weeks were randomly divided into 9groups,8 rats in each group: chow diet group(chow diet),HFD group(HFD),metformin group(0.28% metformin + HFD),4 dosages goat milk group(2.5%,5%,10%,and 30% goat milk power + HFD),30% cow milk group(30% cow milk powder + HFD),goat milk with the chow diet group.The feeding lasted for 20 weeks.Fasting blood glucose was measured at weeks 0,4,8,12,16 and 20.At week 18,the ITT was conducted,and at week 19,the OGTT was conducted.At week 20,the rats were killed.The levels of CHO,TG,HDL,LDL,HbA1 c,adiponectin,leptin,insulin,GLP-1,and PYY in serum were measured.The protein expression of AMPK,PEPCK,and G6 Pase in the liver,and the expression levels of AMPK,GLUT4 and hexokinase2 in the skeletal muscle were detected by western blot.Hepatic portal vein blood was collected to analyze short chain fatty acids.The colonic contents were collected to analyze the gut microbiota and short chain fatty acids.Results1.The effects of goat milk on STZ-induced T1D:(1)On days 0,15 and 30,blood glucose levels of the STZ group were significantly higher than that of the control group(P<0.05).On day 30,the blood glucose level of the high-dose goat milk intervention group was significantly lower than that of the STZ group(P<0.05).The areas under the curve(AUC)of OGTT and ITT in the STZ group were significantly higher than that of the control group(P<0.05),however,compared with the STZ group,the high-dose goat milk intervention could decrease the AUC of OGTT and ITT.(2)When compared with the control group,the HbA1 c level in the STZ group was higher(P<0.05).Compared with the STZ group,the HbA1 c levels of the medium-and high-dose goat milk intervention groups were significantly decreased(P<0.05).When compared with the control group,the insulin and GLP-1 levels in the STZ group were significantly lower(P<0.05),but TNF-? level was significantly higher(P<0.05).Compared with the STZ group,the insulin concentration in the high-dose goat milk intervention group was significantly increased(P<0.05);the concentrations of TNF-? in the medium-and high-dose goat milk intervention groups were significantly decreased(P<0.05);the GLP-1 concentrations of low-and high-dose goat milk intervention groups were significantly increased(P<0.05).(3)Compared with the control group,the p-AMPK/AMPK ratio in the liver and skeletal muscle in the STZ group was higher.Compared with the STZ group,the p-AMPK/AMPK ratio in the high-dose goat milk intervention group was significantly higher(P<0.05).The expression levels of PEPCK and G6 Pase in the liver of the STZ group were significantly higher than that of the control group(P<0.05).The PEPCK levels in the high-dose goat milk intervention group and the cow milk intervention group were significantly lower than that of the STZ group(P<0.05).(4)Compared with the control group,the relative abundance of Lachnospiracea incertae sedis and Parabacteroides were significantly increased in the STZ group,meanwhile,Lactobacillus abundance in the STZ group was significantly decreased.However,after high-dose goat milk intervention,the relative abundance of Lachnospiracea incertae sedis and Parabacteroides were decreased(P<0.05),and the relative abundance of Lactobacillus was increased(P<0.05).(5)Concentrations of propionic acid and butyric acid in the high-dose goat milk intervention group were significantly higher than that in the STZ group(P<0.05).2.The effects of goat milk on HFD induced glucose metabolism disorder:(1)From the week 12 to week 20,the blood glucose of HFD rats was significantly higher than that of the control group(P<0.05).On week 16,the blood glucose level in the10% goat milk intervention group was significantly lower than that in the HFD group(P<0.05).On week 20,the blood glucose levels of the 10% and 30% goat milk intervention groups were significantly lower than that of the HFD group(P<0.05).(2)The AUC of OGTT and ITT in the HFD group were significantly higher than that of the control group(P<0.05).The OGTT AUC in the 10% and 30% goat milk intervention group were significantly smaller than that of the HFD group(P<0.05).Compared with the HFD group,the ITT AUC in the 10% goat milk intervention group were decreased.(3)Compared with the control group,the TG level in the HFD group was significantly increased(P<0.05).The TG concentrations of the 5%,10%,30% goat milk intervention groups and 30% cow milk intervention group were significantly lower than those of the HFD group(P<0.05).The leptin level of the HFD group was significantly higher than that of the control group(P<0.05),and after 5% and 10% goat milk intervention,leptin levels were significantly decreased(P<0.05).The concentration of GLP-1 in the HFD group was significantly lower than that in the control group(P<0.05),and after 5% goat milk intervention,the concentration of GLP-1 was significantly increased(P<0.05).(4)Compared with the control group,the p-AMPK/AMPK ratio the liver and skeletal muscle in the HFD group was reduced.After 10% and 30% goat milk intervention,the ratio was significantly increased(P<0.05).The expression levels of PEPCK in liver of the 10%and 30% goat milk intervention groups were significantly lower than that of the HFD group(P<0.05).The expression of G6 Pase in the liver of the HFD group was significantly higher than that of the control group,and after 30% goat milk intervention the expression of G6 Pase was significantly decreased(P<0.05).The expression of hexokinase2 in the skeletal muscle of the HFD group was significantly lower than that in the control group(P<0.05),and after10% and 30% goat milk intervention the hexokinase2 expression was significantly increased(P<0.05).(5)Compared with the control group,the relative abundance of Lactobacillus and Olsenella in the HFD group were significantly lower(P<0.05),however,after 30% goat milk and 30% cow milk intervention the relative abundance of Lactobacillus and Olsenella was increased(P<0.05).Compared with the control group,the relative abundance of Bacteroides,Clostridium Xl Vb,Erysipelotrichaceae incertae sedis,Mucispirillum,Oxalobacter,Parabacteroides,Sutterella in the HFD group was significantly higher(P<0.05),but after 10%,30% goat milk and 30% cow milk intervention,the relative abundance of Bacteroides,Clostridium Xl Vb,Mucispirillum,Parabacteroides,Sutterella were significantly decreased(P<0.05).In addition,after 10% and 30% goat milk intervention the abundance of Erysipelotrichaceae incertae sedis was significantly decreased(P<0.05),and after 10% goat milk intervention the abundance of Oxalobacter was significantly decreased(P<0.05).(6)Compared with the control group,the levels of colon acetic acid,propionic acid,butyric acid,isobutyric acid and valeric acid in the HFD fed rats were significantly decreased(P<0.05).The levels of acetic acid,propionic acid,butyric acid and isobutyric acid in the colon of the 10% goat milk intervention group were significantly higher than that of the HFD group(P<0.05),meanwhile,the level of isobutyric acid in the colon of the 30%goat milk intervention group was significantly increased(P<0.05),moreover,the propionic acid of the 30% cow milk intervention group was significantly increased(P<0.05).Compared with the control group,the levels of propionic acid and butyric acid in hepatic portal vein of rats fed with HFD were significantly decreased(P<0.05).However,the level of butyric acid in hepatic portal vein in the 10% goat milk intervention group was significantly higher than that of the HFD group(P<0.05).ConclusionGoat milk consumption can improve STZ-induced type 1 diabetes,as well as improve the glucose disorder induced by HFD.Goat milk can improve blood glucose homeostasis,which may be because goat milk can regulate the gut microbiota,and increase the level of short-chain fatty acids and activate the AMPK pathways in the liver and skeletal muscle.