Study On The Role Of Sheep Milk In Regulating Glucose Metabolism

Sheep milk is rich in fat,protein,vitamins and minerals and is also an important source of natural bioactive substances.Studies have found that sheep milk contains many bioactive peptides with antibacterial,antiviral and anti-inflammatory properties that can prevent type 2 diabetes(T2D),Alzheimer’s disease and cancer1.Based on this,an experiment was conducted using sheep milk as the experimental basis.By detecting changes in mouse serological indicators,glucose tolerance(iGTT),key protein expression of sugar and lipid metabolism,and intestinal microorganisms,it was found that sheep milk can regulate mouse glucose metabolism by insulin resistance.The main research content and results are as follows:(1)By detecting the conventional nutritional components of sheep milk and cow milk,it was found that the fat,protein,dry matter and non-fat solids in sheep milk were significantly higher than those in cow milk(P<0.01);Metabolomics sequencing data found that most of the differential metabolites between sheep milk and cow milk were related to lipid metabolism.(2)The regulatory effect of sheep milk on blood glucose and insulin resistance in mice:8week-old male C57BL/6J mice were randomly divided into three groups,each group was fed a high-fat diet for 4 weeks,and sheep milk and cow milk were supplemented with food(0.01 g/day/dry matter per mouse).The grouping situation is the control group(feeding HFD),the sheep milk group(feeding HFD+sheep milk)and the cow milk group(feeding HFD+cow milk).The results showed that compared with the control group,the food intake of mice in the sheep milk group and the cow milk group decreased significantly(P<0.01).The glucose tolerance test results showed that compared with the cow milk group,the tolerance of mice in the sheep milk group to glucose was significantly increased(P<0.01).This experiment initially found that compared with dietary supplementation with cow milk,dietary supplementation with sheep milk can improve the glucose tolerance of insulin-resistant model mice.(3)The regulatory effect of sheep milk on blood glucose and insulin resistance in mice through the intestinal-liver axis:8-week-old male C57BL/6J mice were randomly divided into three groups,each group was fed a high-fat diet for 4 weeks,and sheep milk was supplemented with food at the same time(0.01 g/day/dry matter per mouse).The grouping situation is the control group(feeding HFD),the sheep milk group(feeding HFD+sheep milk)and metformin group(feeding HFD+metformin).Colon H&E staining results showed that compared with negative control group and metformin group mice,intestinal wall thickness increased and macrophage infiltration decreased in mice fed with sheep milk.16s rDNA results of colon contents showed that Akkermansia muciniphila accounted for 45.27%of the total flora in mouse gut microbiota in the sheep milk group;while Akkermansia muciniphila accounted for 31.46%of the total flora in the control group;metformin group accounted for only 0.95%of total flora.The results of the glucose clamp test showed that the glucose infusion rate(GIR)of mice in the sheep milk and metformin groups increased by 29.10%and 33.92%,respectively,compared to the control group;and the GIR of mice in the sheep milk group decreased by 3.60%compared to the metformin group.In addition,endogenous glucose production(EGP)was highly significantly reduced in the sheep milk group compared to the control group(P<0.01);and EGP was significantly reduced in the sheep milk group compared to the metformin group(P<0.05).EGP inhibition increased by 51.43%in the sheep milk group compared to the control group;by 11.23%in the metformin group;and by 43.35%in the sheep milk group compared to the metformin group.The results of the study on the expression of enzymes related to gluconeogenesis and glycolysis in liver tissues showed that the expression of phosphoenolpyruvate carboxykinase(PEPCK),which promotes gluconeogenesis,was significantly lower in the liver tissues of both the sheep milk and metformin groups compared to the control group(P<0.01).The expression of hexokinase 2(HK2)(P<0.05),hexokinase 1(HK1),hexokinase 3(HK3)and glucose-6-phosphate isomerase(Gpi)were significantly increased in the liver tissues of mice from the sheep milk and metformin groups compared to the control group(P<0.01);the expression of fructose diphosphate aldolase(Aldoa)was significantly increased(P<0.005).This experiment demonstrates that dietary supplementation of sheep milk regulates the gut microbiota in insulin-resistant mouse models and alleviates intestinal inflammation,thereby modulating insulin resistance.Simultaneously,it suppresses gluconeogenesis and promotes glycolysis in liver tissues by regulating the expression of enzymes involved in these processes,resulting in decreased blood glucose levels.In summary,sheep milk is rich in nutrients.Dietary supplementation of sheep milk can increase the abundance of Akkermansia in the colonic contents of insulin-resistant mouse models,thereby reducing colon damage.It also enhances the expression of enzymes related to inhibiting gluconeogenesis and promoting glycolysis in liver tissues.This study provides a theoretical basis for the development of sheep milk-based specialized medical food for blood glucose regulation.