Genistein and daidzein modulate hepatic glucose and lipid regulating enzyme activities in C57BL/KsJ-db/db mice

This study examines whether anti-diabetic effects of genistein and daidzein are mediated by hepatic glucose and lipid regulating enzyme activities in type 2 diabetic animals. Male C57BL/KsJ-lepr(db)/lepr(db) (db/db) mice and age-matched non-diabetic littermates (db/+) were used in this study. The db/db mice were divided into control, genistein (0.02%, w/w) and daidzein (0.02%, w/w) groups. The blood glucose and HbA(1c) levels were significantly lower in the genistein and daidzein groups than in the control group, while glucose tolerance only was significantly improved in the genistein-supplemented group. The plasma insulin and C-peptide levels did not differ significantly between groups, yet the glucagon level was lower in the genistein and daidzein groups compared to that in the control db/db or db/+ group. The genistein and daidzein supplements increased the insulin/glucagon ratio in the type 2 diabetic animals. While the hepatic glucokinase activity was significantly lower in the db/db control group, the glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities were significantly higher in the control group compared to the db/+ group. Interestingly, these hepatic glucose metabolizing enzyme activities were reversed by the genistein and daidzein supplementation in db/db mice compared to the control group. The hepatic fatty acid synthase, beta-oxidation and carnitine palmitoyltransferase activities were all significantly lower in the genistein and daidzein groups than in the control group. The genistein and daidzein supplements also improved the plasma total cholesterol, triglyceride, HDL-cholesterol/total cholesterol, free fatty acid and hepatic triglyceride concentrations in the db/db mice. These results suggest that genistein and daidzein exert anti-diabetic effect in type 2 diabetic conditions by enhancing the glucose and lipid metabolism.     

Altered macrophage function is associated with severe Burkholderia pseudomallei infection in a murine model of type 2 diabetes

This study used a murine model of type 2 diabetes (BKS.Cg-Dock7(m) +/+Lepr(db)/J mice) to investigate the inflammatory and cellular mechanisms predisposing to Burkholderia pseudomallei infection and co-morbid diabetes. Homozygous db/db (diabetic) mice developed extreme obesity, dyslipidaemia and glucose intolerance leading to hyperglycaemia and overt type 2 diabetes. Compared to their heterozygous db/+ (non-diabetic) littermates, diabetic mice rapidly succumbed to subcutaneous B. pseudomallei infection, paralleled by severe hypoglycaemia and increased expression of the proinflammatory cytokines, tumour necrosis factor (TNF)-α and interleukin (IL)-1β, in the spleen, despite comparable bacterial loads in the spleen of non-diabetic mice. Neutrophil oxidative burst and dendritic cell uptake and killing of B. pseudomallei were similar between diabetic and non-diabetic mice. Compared to peritoneal macrophages from non-diabetic mice, macrophages from diabetic mice were unable to contain and kill B. pseudomallei. Functional differences between macrophages of diabetic and non-diabetic mice toward B. pseudomallei may contribute to rapid dissemination and more severe disease progression in hosts with co-morbid type 2 diabetes.     

MRNA and enzyme activity of hepatic 11beta-hydroxysteroid dehydrogenase type 1 are elevated in C57BL/KsJ-db/db mice.

To evaluate the importance of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in insulin resistant diabetic C57BL/KsJ-db/db mice, we measured the activity and mRNA level of 11beta-HSD1 in the liver of db/db mice and their heterozygote litter mates, db/+m mice. The blood glucose, plasma insulin, and corticosterone levels of db/db mice were significantly higher than those of db/+m mice. Despite hyperinsulinemia, the activity level of this enzyme was significantly higher in db/db mice, and the mRNA level of hepatic 11beta-HSD1 was also significantly higher in db/db mice. Since hepatic 11beta-HSD1 in vivo mainly functions as 11-keto-reductase and does not work as 11beta-oxidase, these results suggest that the rate of hepatic conversion of 11-dehydrocorticosterone to corticosterone is increased in db/db mice, resulting in higher glucocorticoid activity in the liver. The increased hepatic corticosterone concentration due to the elevation of 11beta-HSD1 and high plasma corticosterone concentration may antagonize the action of insulin and cause insulin resistance. These findings have a potentially important implication for relationships between increased hepatic 11beta-HSD1 and insulin resistance in db/db mice. The present paper is the first to demonstrate the increased activities and mRNA level of hepatic 11beta-HSD1 in db/db mice.     

Dehydroepiandrosterone decreases elevated hepatic glucose production in C57BL/KsJ-db/db mice

Dehydroepiandrosterone (DHEA) is known to improve hyperglycemia in diabetic db/db mice that are obese and insulin resistant. In a previous study, we reported that DHEA suppresses the elevated hepatic gluconeogenic glucose-6-phosphatase (G6Pase) activity and gene expression in C57BL/KsJ-db/db mice. In the present study, we evaluated the total amount of gluconeogenesis using NaH[(14)C]CO(3) and hepatic glucose production using fructose as a substrate in primary cultured hepatocytes. Despite hyperinsulinemia, the glucose production of db/db mice in the total body and hepatocytes was elevated as compared to their heterozygote littermate C57BL/KsJ-db/+m mice. Administration of DHEA significantly decreased the blood glucose level and increased the plasma insulin level in db/db mice. Administration of DHEA decreased the elevated total body and hepatic glucose production in db/db mice. In addition, the glucose production in the primary cultured hepatocytes of db/db mice was decreased significantly by the direct addition of DHEA or DHEA-S to the medium. These results suggest that administration of DHEA suppresses the elevated total body and hepatic glucose production in db/db mice, and this effect on the liver is considered to result from increased plasma insulin and DHEA or DHEA-S itself.     

Tertiary butylhydroquinone alleviates gestational diabetes mellitus in C57BL/KsJ-Lep db/+ mice by suppression of oxidative stress

Gestational diabetes mellitus (GDM) is a common disorder characterized by abnormal glucose metabolism during pregnancy, affecting 2% to 5% of pregnant women. Currently, clinical treatment for GDM is very limited. The present study was designed to investigate the effect and underlying molecular mechanism of tertiary butylhydroquinone (TBHQ) in a pregnant C57BL/KsJ-Lep db/+ (referred to as db+) GDM mouse model. The results showed that nonpregnant db/+ mice did not show a diabetic phenotype, and TBHQ had no effect on glucose and insulin tolerance in these mice. Moreover, in db/+ pregnant mice exhibiting typical diabetes symptoms, such as hyperglycemia and hypoinsulinemia, TBHQ could remarkably decrease the blood glucose level, increase insulin level, and improve glucose and insulin intolerance. The results also revealed that TBHQ could inhibit oxidative stress in pregnant db/+ mice. Furthermore, TBHQ greatly improved offspring survival rate, glucose metabolism, and insulin tolerance. In addition, TBHQ inhibited oxidative stress by reducing malondialdehyde (MDA) and reactive oxygen species (ROS) levels and increased superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. Moreover, we found that TBHQ activated the nuclear factor erythroid 2-related factor 2 (Nrf2), thereby increasing the levels of Nrf2, and ultimately upregulating the expression of heme oxygenase 1 (NO-1) and superoxide dismutase 2 (SOD2). In conclusion, our findings demonstrated that TBHQ alleviated GDM via Nrf2 activation.     

Elevated Expression of Carboxy-Terminal Modulator Protein (CTMP) Aggravates Brain Ischemic Injury in Diabetic db/db Mice

Deregulation of Akt signaling is important in the brain injuries caused by cerebral ischemia in diabetic animals, and the underlying mechanism is not fully understood. We investigated the role of carboxy-terminal modulator protein (CTMP), an endogenous Akt inhibitor, in brain injury following focal cerebral ischemia in type 2 diabetic db/db mice and their control littermates non-diabetic db/+ mice. db/db mice showed a significant elevation in the expression of CTMP compared to db/+ mice under normal physiological conditions. After ischemia, db/db mice exhibit higher levels of CTMP expression, decreased Akt kinase activity, adverse neurological deficits and cerebral infarction than db/+ mice. To further certain the effectiveness of Akt signaling to the final outcome of cerebral ischemia, the animals were treated with LY294002, an inhibitor of the Akt pathway, which aggravated the ischemic injury in db/+ mice but not in db/db mice. RNA interference-mediated depletion of CTMP were finally applied in db/db mice, which restored Akt activity, improved neurological scores and reduced infarct volume. These results suggest that elevation of CTMP in diabetic mice suppresses Akt activity and ultimately negatively affects the outcome of ischemia. Inhibitors specifically targeting CTMP may be beneficial in the treatment of cerebral ischemia in patients with diabetes.     

Increased Aβ production prompts the onset of glucose intolerance and insulin resistance

Type 2 diabetes (T2D) mellitus and Alzheimer's disease (AD) are two prevalent diseases with comparable pathophysiological features and genetic predisposition. Patients with AD are more susceptible to develop T2D. However, the molecular mechanism linking AD and T2D remains elusive. In this study, we have generated a new mouse model to test the hypothesis that AD would prompt the onset of T2D in mice. To test our hypothesis, we crossed Alzheimer APPswe/PS1dE9 (APP/PS1) transgenic mice with mice partially deficient in leptin signaling (db/+). Body weight, plasma glucose, and insulin levels were monitored. Phenotypic characterization of glucose metabolism was performed using glucose and insulin tolerance tests. β-Cell mass, islet volume, and islet number were analyzed by histomorphometry. APP/PS1 coexpression in mice with intact leptin receptor signaling did not show any metabolic perturbations in glucose metabolism or insulin sensitivity. In contrast, APP/PS1 coexpression in db/+ mice resulted in nonfasting hyperglycemia, hyperinsulinemia, and hypercholesterolemia without changes in body weight. Conversely, fasting blood glucose and cholesterol levels remained unchanged. Coinciding with altered glucose metabolism, APP/PS1 coexpression in db/+ mice resulted in glucose intolerance, insulin resistance, and impaired insulin signaling. In addition, histomorphometric analysis of pancreata revealed augmented β-cell mass. Taken together, these findings provide experimental evidence to support the notion that aberrant Aβ production might be a mechanistic link underlying the pathology of insulin resistance and T2D in AD.     

Glucose and insulin improve cardiac efficiency and postischemic functional recovery in perfused hearts from type 2 diabetic (db/db) mice

Hearts from type 2 diabetic (db/db) mice demonstrate altered substrate utilization with high rates of fatty acid oxidation, decreased functional recovery following ischemia, and reduced cardiac efficiency. Although db/db mice show overall insulin resistance in vivo, we recently reported that insulin induces a marked shift toward glucose oxidation in isolated perfused db/db hearts. We hypothesize that such a shift in metabolism should improve cardiac efficiency and consequently increase functional recovery following low-flow ischemia. Hearts from db/db and nondiabetic (db/+) mice were perfused with 0.7 mM palmitate plus either 5 mM glucose (G), 5 mM glucose and 300 microU/ml insulin (GI), or 33 mM glucose and 900 microU/ml insulin (HGHI). Substrate oxidation and postischemic recovery were only moderately affected by GI and HGHI in db/+ hearts. In contrast, GI and particularly HGHI markedly increased glucose oxidation and improved postischemic functional recovery in db/db hearts. Cardiac efficiency was significantly improved in db/db, but not in db/+ hearts, in the presence of HGHI. In conclusion, insulin and glucose normalize cardiac metabolism, restore efficiency, and improve postischemic recovery in type 2 diabetic mouse hearts. These findings may in part explain the beneficial effect of glucose-insulin-potassium therapy in diabetic patients with cardiac complications.     

A Tripeptide Diapin Effectively Lowers Blood Glucose Levels in Male Type 2 Diabetes Mice by Increasing Blood Levels of Insulin and GLP-1

The prevalence of type 2 diabetes (T2D) is rapidly increasing worldwide. Effective therapies, such as insulin and Glucagon-like peptide-1 (GLP-1), require injections, which are costly and result in less patient compliance. Here, we report the identification of a tripeptide with significant potential to treat T2D. The peptide, referred to as Diapin, is comprised of three natural L-amino acids, GlyGlyLeu. Glucose tolerance tests showed that oral administration of Diapin effectively lowered blood glucose after oral glucose loading in both normal C57BL/6J mice and T2D mouse models, including KKay, db/db, ob/ob mice, and high fat diet-induced obesity/T2D mice. In addition, Diapin treatment significantly reduced casual blood glucose in KKay diabetic mice in a time-dependent manner without causing hypoglycemia. Furthermore, we found that plasma GLP-1 and insulin levels in diabetic models were significantly increased with Diapin treatment compared to that in the controls. In summary, our findings establish that a peptide with minimum of three amino acids can improve glucose homeostasis and Diapin shows promise as a novel pharmaceutical agent to treat patients with T2D through its dual effects on GLP-1 and insulin secretion.     

Hepatic phase II biotransformation in C57Bl/KsJ db/db mice: comparison to that in Swiss Webster and 129 REJ mice

1. Cytochrome P-450 concentrations were similar in male and female carrier (db/+) and diabetic (db/db) mice. Benzphetamine N-demethylase and styrene oxide hydrolase activities were 47 and 65% lower in db/+ than in db/db mice. 2. UDP-Glucuronosyltransferase activity toward 1-naphthol, estrone and diethylstilbestrol was not different between db/db and db/+, but was 40% higher in db/db mice toward testosterone. 3. Glutathione S-transferase activity toward 1-chloro-2,4-dinitrobenzene and ethacrynic acid was 47 and 59% lower in db/db mice than in male db/+ mice. Female db/+ mice had similar activities to those found in diabetic animals. 4. The differences in enzyme activity between hyperinsulinemic and normal animals suggest that insulin can influence both phase I and phase II biotransformations. 5. Enzyme activities in db/+ and db/db mice were compared to those in 129 REJ and Swiss Webster mice.     

Coxsackievirus B infection in the mouse: Effects associated with the diabetes gene,db

Coxsackievirus B4 (CB4) replicated to equally high titers in the pancreas and other tissues of the C57BL/Ks (+/+) mouse and its genetic variants that were either heterozygous (db/+) or homozygous (db/db) for the autosomal recessive gene for diabetes, db. In contrast, the insulin-producing beta cells of both diabetic variants, but not the +/+ mice, completely degranulated during acute infection and resulted in hypoglycemia and hyperinsulemia. All db/db mice died within 13 days, with signs of severe endocrine pancreas involvement. Surviving +/+ mice maintained relatively normal glucose homeostasis. Surviving db/+ variants exhibited prolonged periods of diabetes-like disease with hypoinsulemia and abnormal glucose tolerance, even though the db gene is not phenotypically expressed in the heterozygous state.     

Augmented lipopolysaccharide-induced TNF-alpha production by peritoneal macrophages in type 2 diabetic mice is dependent on elevated glucose and requires p38 MAPK

Dysregulated inflammation is a complication of type 2 diabetes (T2D). In this study, we show that augmented LPS-induced TNF-alpha production by resident peritoneal macrophages (PerMphi) in type 2 diabetic (db/db) mice is dependent on elevated glucose and requires p38 MAPK. Intraperitoneal LPS administered to db/db and nondiabetic (db/+) mice induced 3- and 4-fold more TNF-alpha in the peritoneum and serum, respectively, of db/db mice as compared with db/+ mice. Examination of the TLR-4/MD2 complex and CD14 expression showed no difference between db/db and db/+ PerMphi. Ex vivo stimulation of PerMphi with LPS produced a similar 3-fold increase in TNF-alpha production in db/db PerMphi when compared with db/+ PerMphi. PerMphi isolated from db/+ mice incubated in high glucose (4 g/L) medium for 12 h produced nearly 2-fold more TNF-alpha in response to LPS than PerMphi incubated in normal glucose medium (1 g/L). LPS-dependent stimulation of PI3K activity, ERK1/2 activation, and p38 kinase activity was greater in PerMphi from db/db mice as compared with db/+ mice. Only inhibition of p38 kinase blocked LPS-induced TNF-alpha production in PerMphi from db/db mice. Taken together, these data indicate that augmented TNF-alpha production induced by LPS in macrophages during diabetes is due to hyperglycemia and increased LPS-dependent activation of p38 kinase.     

Effects of antidiabetic drugs on glucose tolerance in streptozotocin-nicotinamide-induced mildly diabetic and streptozotocin-induced severely diabetic mice

In this study, streptozotocin-nicotinamide-induced mildly diabetic mice and streptozotocin-induced severely diabetic mice were created to compare their characteristics and to investigate the effects of antidiabetic drugs on glucose tolerance. In severely diabetic mice, the pancreatic insulin content decreased to approximately 10% of levels found in normal mice. These mice also showed a decrease in body weight, a marked increase in nonfasting blood glucose levels and urinary glucose excretion, and a marked decline in glucose tolerance due to insulin secretory deficiency. In contrast, the pancreatic insulin content was approximately 50% of normal levels in mildly diabetic mice. These mice did not show any change in body weight, but displayed a mild increase in nonfasting blood glucose levels and urinary glucose excretion, and a mild decline in glucose tolerance due to loss of early-phase insulin secretion. Administration of antidiabetic drugs, namely voglibose, metformin, glibenclamide, sitagliptin and insulin, significantly improved glucose tolerance in mildly diabetic mice. In severely diabetic mice, voglibose, metformin and insulin significantly improved glucose tolerance, but no significant effect was observed for glibenclamide and sitagliptin due to a decreased insulinotropic effect. These results demonstrate that streptozotocin-nicotinamide-induced mildly diabetic mice have many pathological features resembling type 2 diabetes, and can serve as models for the pharmacological evaluation of many antidiabetic drugs.     

Astaxanthin protects beta-cells against glucose toxicity in diabetic db/db mice

Oxidative stress induced by hyperglycemia possibly causes the dysfunction of pancreatic beta-cells and various forms of tissue damage in patients with diabetes mellitus. Astaxanthin, a carotenoid of marine microalgae, is reported as a strong anti-oxidant inhibiting lipid peroxidation and scavenging reactive oxygen species. The aim of the present study was to examine whether astaxanthin can elicit beneficial effects on the progressive destruction of pancreatic beta-cells in db/db mice--a well-known obese model of type 2 diabetes. We used diabetic C57BL/KsJ-db/db mice and db/m for the control. Astaxanthin treatment was started at 6 weeks of age and its effects were evaluated at 10, 14, and 18 weeks of age by non-fasting blood glucose levels, intraperitoneal glucose tolerance test including insulin secretion, and beta-cell histology. The non-fasting blood glucose level in db/db mice was significantly higher than that of db/m mice, and the higher level of blood glucose in db/db mice was significantly decreased after treatment with astaxanthin. The ability of islet cells to secrete insulin, as determined by the intraperitoneal glucose tolerance test, was preserved in the astaxanthin-treated group. Histology of the pancreas revealed no significant differences in the beta-cell mass between astaxanthin-treated and -untreated db/db mice. In conclusion, these results indicate that astaxanthin can exert beneficial effects in diabetes, with preservation of beta-cell function. This finding suggests that anti-oxidants may be potentially useful for reducing glucose toxicity.     

Effect of murine cytomegalovirus on the in vitro responses of T and B cells to mitogens.

Both in vitro and in vivo murine cytomegalovirus (MCMV) infection depressed the responses of lymphocytes to both B and T cell mitogens. The possibilities that macrophages or nonspecific T cell inhibition of B cells might account for the depressed responses were eliminated. In vitro data suggested that B cell responses are more susceptible to this depression than T cell responses. The possibility that the depression of T cell responses is not a direct effect of viral infection of lymphocytes is discussed. To investigate further the interaction between B and T lymphocytes and MCMV, mice with B and T cell deficiences were studied. A comparison of the susceptibility of athymic Nu/Nu mice and T cell competent Nu/+ littermates to MCMV showed that the LD50 for Nu/Nu mice is 10-fold lower than that for Nu/+ mice, but Nu/+ mice given an LD50 of virus died much sooner after infection than Nu/Nu mice given an LD50. Pathogenic mechanisms responsible for death may be different in these two groups of mice. Similarly the MCMV LD50 for B cell-deficient mice (treated with goat anti-mouse IgM serum) was 10-fold lower than the LD50 for mice treated with normal goat serum, but given an LD50 of virus, the latter died sooner after infection than the former. In contrast, there was little difference between the LD50 or time of death after MCMV infection of CBA x DBA F1 male mice (which are deficient in their response to thymic independent antigens) and their normal littermates, the CBA x DBA F1 female mice.     

Structural and functional analysis of pancreatic islets preserved by pioglitazone in db/db mice

To evaluate preventive effects of pioglitazone on pancreatic beta-cell damage in C57BL/KsJ db/db mice, an obese diabetic animal model, the pancreatic islets were compared morphologically between pioglitazone-treated (100 mg/kg daily po) and untreated db/db mice (n = 7 for each) after a 12-wk intervention (6-18 wk of age). The fasting blood glucose level was significantly improved by the treatment with pioglitazone (260 +/- 12 vs. 554 +/- 62 mg/dl, P < 0.05). The islet mass in the pancreas was significantly greater in pioglitazone-treated mice than in untreated mice (10.2 +/- 1.1 vs. 4.6 +/- 0.2 mg, P < 0.01). Subsequently, biochemical and physiological analyses of the beta-cell function were employed using pioglitazone-treated and untreated db/db mice (n = 6 for each) and pioglitazone-treated and untreated db/+ mice (n = 6 for each). After 2 wk of treatment (10-12 wk of age), the plasma levels of triglyceride and free fatty acid were significantly decreased, whereas the plasma adiponectin level increased significantly compared with the untreated group (65.2 +/- 18.0 vs. 18.3 +/- 1.3 microg/ml, P < 0.05). Pioglitazone significantly reduced the triglyceride content in the islets (43.3 +/- 3.6 vs. 65.6 +/- 7.6 ng/islet, P < 0.05) with improved glucose-stimulated insulin secretion. Pioglitazone showed no significant effects on the biochemical and physiological parameters in db/+ mice. The present study first demonstrated that pioglitazone prevents beta-cell damage in an early stage of the disease progression in db/db mice morphologically and physiologically. Our results suggest that pioglitazone improves glucolipotoxicity by increasing insulin sensitivity and reducing fat accumulation in the pancreatic islets.     

Activation of insulin signal transduction pathway and anti-diabetic activity of small molecule insulin receptor activators

We recently described the identification of a non-peptidyl fungal metabolite (l-783,281, compound 1), which induced activation of human insulin receptor (IR) tyrosine kinase and mediated insulin-like effects in cells, as well as decreased blood glucose levels in murine models of Type 2 diabetes (Zhang, B., Salituro, G., Szalkowski, D., Li, Z., Zhang, Y., Royo, I., Vilella, D., Diez, M. T. , Pelaez, F., Ruby, C., Kendall, R. L., Mao, X., Griffin, P., Calaycay, J., Zierath, J. R., Heck, J. V., Smith, R. G. & Moller, D. E. (1999) Science 284, 974-977). Here we report the characterization of an active analog (compound 2) with enhanced IR kinase activation potency and selectivity over related receptors (insulin-like growth factor I receptor, epidermal growth factor receptor, and platelet-derived growth factor receptor). The IR activators stimulated tyrosine kinase activity of partially purified native IR and recombinant IR tyrosine kinase domain. Administration of the IR activators to mice was associated with increased IR tyrosine kinase activity in liver. In vivo oral treatment with compound 2 resulted in significant glucose lowering in several rodent models of diabetes. In db/db mice, oral administration of compound 2 elicited significant correction of hyperglycemia. In a streptozotocin-induced diabetic mouse model, compound 2 potentiated the glucose-lowering effect of insulin. In normal rats, compound 2 improved oral glucose tolerance with significant reduction in insulin release following glucose challenge. A structurally related inactive analog (compound 3) was not effective on insulin receptor activation or glucose lowering in db/db mice. Thus, small molecule IR activators exert insulin mimetic and sensitizing effects in cells and in animal models of diabetes. These results have implications for the future development of new therapies for diabetes mellitus.     

Increased turnover of surface insulin receptors in fibroblastic cultures from genetically diabetic (DB/DB) mice

The turnover of surface insulin receptors in fibroblastic cultures from genetically diabetic (db/db) mice and nondiabetic (m/m) littermates has been determined by combining a heavy isotope density shift technique with cross-linking of insulin to surface receptors. Our results indicate that the surface insulin receptors turn over faster in diabetic cells than in nondiabetic cells. In addition, fewer receptors are incorporated into the plasma membrane per hour in diabetic cells than in nondiabetic cells. It is possible to propose a model to account for the altered expression of surface insulin receptors in diabetic cells on the basis of abnormalities of receptor incorporation and turnover.     

十两茶水提物降糖作用及机制研究

探讨了湖南安化黑茶的主要品种十两茶水提物的降糖作用及机制.选用6～8周龄db/db自发性糖尿病模型小鼠,每日灌胃给予3个不同剂量的十两茶水提物(100、200、400 mg/kg),连续28 d.每周测定空腹血糖值,实验结束时检测糖耐量和胰岛素水平.研究结果显示,十两茶水提物400 mg/kg给药28 d就能显著降低db/db糖尿病小鼠空腹血糖和改善其对葡萄糖耐受能力.同时,十两茶水提物能显著降低db/db糖尿病小鼠血清胰岛素水平,增加葡萄糖耐量试验胰岛素的释放.结果显示十两茶水提物对2型糖尿病小鼠具有很好的降糖作用,其作用机制与增加胰岛素敏感性有关.