Salivary gland dysfunction is a common complication of diabetes. Decreased saliva production and changes in saliva composition may cause oral diseases. Reactive oxygen species (ROS) generation in the salivary glands results in the loss of acinar cells and decreased saliva secretion. Glucagon-like peptide 1 (GLP-1) is the incretin hormone that regulates blood glucose level and can suppress ROS production and inflammation through its antioxidant effects. Dipeptidyl peptidase-4 (DPP-4) is an enzyme that breaks down GLP-1. In this study, we evaluated the pathological role of DPP-4 and GLP-1 on salivary gland dysfunction in type 2 diabetic db/db mice. We observed reduced salivary secretion and histopathological alteration of salivary glands in the db/db mice. The increased DPP-4 and decreased GLP-1 levels in the salivary glands were also detected in the db/db mice. Furthermore, the db/db mice had increased apoptosis and oxidative injury in salivary glands. There was an accumulation of advanced glycation end products and mucus in the salivary glands of the db/db mice. In conclusion, these results showed the possible involvement of DPP-4 and GLP-1, leading to increased ROS-induced apoptosis in diabetes-related salivary gland dysfunction. DPP-4 and GLP-1 may be a pharmacological target for patients with diabetes-related salivary gland dysfunction.

본 연구의 목적은 내당능장애를 유도한 쥐들을 대상으로 다른 운동 강도의 지구성 및 저항 성 운동을 중재하여 당뇨관련 혈액인자들에 미치는 영향을 비교 분석하는데 있다. 37주령 C57BL/6 쥐 54마리를 (1) 일반식이대조군(CO, n=9), (2) 내당능장애군(IGT, n=9), (3) 내당능장애 + VO2max 50% 지구성운동군(IGT50A, n=9), (4) 내당능장애 + VO2max 75% 지구성운동군(IGT75A, n=9), (5) 내당능 장애 + 1RM의 50% 저항성운동군(IGT50R, n=9), 그리고 (6) 내당능장애 + 1RM의 75% 저항성운동군(IGT75R, n=9)으로 분류하였다. 지구성 운동 프로그램은 동물 실험용 트레드밀을 사용하여 주5일, 1일 40분씩 8주간 트레드밀운동을 실시하였다. 저항성 운동은 주5일 8주간 사다리 저항 운동을 반복사이 2분간의 휴식을 주어 총 8번의 Climbing을 실시하였다. 운동 프로그램 후 인슐린은 통계적으로 모든 그룹간의 차이가 없었다. 공복 혈당은 대조군보다 IGT 유도군들에서 통계적으로 유의하게 높게 나타났으며, 운동군들간의 차이는 없었으나 IGT군이 IGT75R군에 비해 유의하게 높은 수치를 보였다. HOMA-IR은 대조군과 IGT군에서만 유의한 차이를 보였다. 당화혈색소 검사에서는 IGT군이 다른 모든 집단들에 비해 높은 수치를 보였으며, IGT75A군과 IGT50R군에서 유의한 차이를 보였다. 총 콜레스 테롤은 대조군이 내당능장애 유도군들과 비교하여 유의하게 낮은 수치를 보여주었다. 반면 중성지방은 그룹간의 차이가 없었다. HDL-C는 지구성 운동군들이 대조군과 IGT군에 비해 유의하게 높은 수치를 보였으나 저항성 운동군들과의 차이는 없었다. LDL-C는 대조군이 IGT군과 운동군들에 비해 유의하게 낮은 수치를 보였으며, IGT75A군은 IGT군과 IGT50R군에 비해 낮은 수치를 보였다. 결론적으로 75%의 저항성 운동은 혈당에 보다 긍정적인 영향을 주었으며, 75%의 지구성 운동은 당화혈색소와 LDL-C 의 감소에 긍정적인 영향을 미치는 것으로 나타났다. 또한 지구성 운동은 저항성 운동에 비해 HDL-C 의 증가에 보다 효과적임을 보여주었다.

본 연구는 서로 다른 운동유형이 당뇨처치 그룹의 베타 아밀로이드, BDNF 및 인지기능에 미치는 영향을 알아보기 위하여 24마리의 C57BL/6 쥐를 당뇨처치를 하지 않은 그룹 6마리(통제그룹: 6)와 당뇨처치 그룹 18마리로 무작위 할당하여, 이를 다시 당뇨처치 그룹의 경우 통제그룹 6마리, 유산소 운동그룹 6마리, 저항운동 그룹 6마리로 나누었고 운동그룹은 8주간 주 5회 저강도로 각각 트레드밀 운동과 사다리 운동을 실시하였다. 그 결과 베타아밀로이드는 8주 후 당뇨처치 그룹의 통제그룹 (DM.G.)이 나머지 세 그룹에 비하여 높은 수준을 나타내었으나 통계적으로 유의한 차이는 나타나지 않았다. BDNF의 경우는 당뇨통제그룹이 나머지 세 그룹에 비하여 낮은 수준을 나타냈으며 통계적으로 유의한 차이를 나타냈다(p<.05). 인지기능을 알아보기 위한 Y-미로 검사에서도 당뇨통제 그룹이 나머지 세그룹에 비하여 낮은 수준을 보였으며 통계적으로도 유의한 차이를 나타냈다(p<.05).

제2형 당뇨 마우스로 8주간 50%, 75% 강도의 유산소성 및 저항성 운동을 수행하여 항 당뇨 및 지질 개선에 미치는 영향을 비교 분석하였다. 39주령 C57BL/6 마우스 48마리를 일반식이정상군 (Normal, n=8)을 제외하고, Streptozotocin (STZ)으로 당뇨를 유발하여 제2형 당뇨군(DM, n=8), 제2형 당뇨+VO2max 50% 유산소운동군(DM50A, n=8), 제2형 당뇨+VO2max 75% 유산소운동군(DM75A, n=8), 제2형 당뇨+1RM 50% 저항운동군(DM50R, n=8), 그리고 제2형 당뇨+1RM 75% 저항운동군 (DM75R, n=8)으로 구분하였다. 유산소성 운동은 주 5일, 1일 40분씩 8주간 트레드밀 운동을 실시하였으며, DM50A군은 1~4주는 8m/min, 5~8주는 8~10m/min으로, DM75A군은 1~4주는 12m/min, 5~8주는 12~14m/min으로 점증하여 실시하였다. 저항성 운동은 주5일 8주간 사다리 저항운동을 실시하였으며, DM50R군은 1RM의 50%, DM75R군은 1RM의 75%로 운동 반복 사이 2분간의 휴식을 주어 총 8번의 Climbing을 실시하였다. 8주간의 운동 후 공복 혈당은 DM군에 비해 DM운동군에서 유의적으로 낮았으 며, 인슐린은 운동에 따른 유의한 차이가 없었으나, HOMA-IR은 DM군에 비해 DM운동군이 유의하게 낮은 것으로 나타났다. HbA1c는 DM군에 비해 DM50R 및 DM75R군이 유의하게 낮은 것으로 나타났다. 총콜레스테롤과 LDL-C는 DM운동군 간의 차이가 없었으나, HDL-C는 DM75A군이 가장 높은 수준으로 나타났고, 중성지방은 DM75R군이 가장 낮게 나타났다. 심혈관 위험 지수는 Normal군 및 DM75A군이 가장 낮게 나타났다. 따라서 T2DM 마우스에서 중강도의 저항성 운동은 혈당 및 인슐린 저항성 조절에 더 나은 개선을 보여주었으며, 중강도의 유산소성 운동은 HDL-C 수준 증가를 통한 심혈관 위험 지수를 감소 하는데 효과적이었다.

The objective of this study was to determine the anti-diabetic effect of the water extract of Neolentinus lepideus in a diabetic mouse model. Seven-week-old C57BL/KsJ-db/db mice were fed either a control diet (CD) or diet supplemented with 1% or 5% of N. lepideus water extract (NLWE1 or NLWE5) for 10 weeks. Oral administration of NLWE significantly decreased the body weight gain compared to that of CD-fed group. Mice in the NLWE group had significantly lower levels of fasting serum glucose, fatty acids, and low-density lipoprotein cholesterol compared to those in the control group. These effects were accompanied by reduced fatty liver and improved glucose tolerance in the NLWE group. Taken together, these results suggest that N. lepideus might have potential as a dietary supplement to control diabetes.

Metabolic syndrome, including obesity, glucose intolerance and elevated blood pressure, is related to type 2 diabetes and cardiovascular disease. Previous studies have reported the anti-oxidative, anti-inflammatory and anti-diabetic effects of purple corn extract. We investigated the efficacy of purple corn extract (PC) against high-fat diet (HFD)-induced obesity and glucose intolerance, and examined the underlying mechanisms by analyzing expression of proteins and genes involved in glucose regulation and macrophage infiltration. C57BL/6 mice were fed with normal chow diet (ND), or HFD treated with distilled water (DW, control) or PC, for 10 weeks. Although body weights were similar in the HFD-fed groups, we observed a decrease in the liver and epididymal adipose tissue (EAT) weights, and enhanced glucose tolerance test (GTT) results in the PC group, as compared with DW group. Liver showed increased Akt phosphorylation in the PC-treated mice; however, no changes were observed in the EAT, for all groups. In PC-treated mice, decreased macrophage infiltration was seen in the EAT, with a reduced expression of macrophage marker genes. Finally, proinflammatory cytokine gene expressions were decreased by PC in the EAT, and a modest trend for downregulation was observed in the liver. Hence, we conclude that PC may decrease glucose intolerance by increasing the phosphorylation of Akt and reducing the macrophage infiltration into the EAT.

This study investigated the antidiabetic effect of amaranth grain ethanol extract (AEE) in a diabetic animal model, db/db mouse. The mice were divided into 4 groups: normal control mice (C57BL/6J), diabetic mice (C57BL/6J db/db), diabetic mice fed a lower concentration of AEE (0.3 mg/kg), and diabetic mice fed a higher concentration of AEE (0.5 mg/kg). After 10 weeks of treatment, body weights, blood insulin levels and blood glucose levels of each group were compared. At the end of treatment, the results showed that both AEE supplemented groups had lower body weights than those in the diabetic groups although higher than those in the normal groups. Moreover, in both AEE supplemented groups, serum insulin levels were higher and blood glucose levels were lower than those in the diabetic groups although both values were higher than those in the normal groups. The results of this study suggest that AEE can alleviate many of the common symptoms of diabetes in diabetic mice and, therefore, has potential as a therapeutic supplement for normalization of blood glucose and insulin levels in humans.

Makgeolli is a health beneficial food for diabetes compared to other alcoholic beverages. We examined the effect of Makgeolli on blood glucose level and survival rate in a streptozotocin (STZ)-induced diabetic mouse model. We force fed 30 male STZ-induced diabetic ICR mice Makgeolli consisting of 6% alcohol (DM-MAK), 6% ethanol (DM-EtOH), or distilled water (DM-DW) for 4 weeks. In the DM-MAK group, food intake and water intake were higher than those of other groups after 4 weeks. Body weight, however, was not different among the experimental groups. We also found no significant difference in blood glucose level among the experimental groups. In normal ICR mice fed Makgeolli for 1 week, the area of the blood glucose curve was higher than those of other groups fed 6% ethanol, 2% glucose, or distilled water. Survival rates of STZ-induced diabetic mice fed Makgeolli, 6% ethanol, or DW for 4 weeks were 100%, 25%, and 62.5%, respectively. In conclusion, Makgeolli had no beneficial effect on blood glucose in a STZ-induced diabetic mouse model, although their survival rate was high. These results show that Makgeolli has an effect on type 1 diabetes through other mechanisms than blood glucose control.

본 연구에서는 자연발증 인슐린 의존성 당뇨병 모델동물인 Non-obese diabetic(NOD) 마우스에게 naringin 보충이 당대사 개선에 미치는 영향을 살펴보고자 하였다. 암컷 NOD 마우스는 정상식이를 섭취한 대조군과 정상식이에 0.02%(w/w)의 naringin 보충식이를 급여한 실험군으로 나누어 11주간 자유식과 자유급수를 통해 사육하였다. naringin 보충은 식이섭취량에는 유의적인 영향을 미치지 않았으나 당뇨로 인한 체중감량, 혈당상승 및 사망을 억제시키는 것으로 나타났다. 또한 내당능을 개선시키고 혈중 인슐린과 C-peptide 농도를 증가시키는 반면 혈중 글루카곤 농도를 감소시켰다. 흥미롭게도 혈중 인슐린과 글루카곤 농도 변화와 일치되게 췌장 인슐린의 단백질 발현이 naringin 보충에 의해 증가하는 반면 췌장 글루카곤의 단백질 발현은 감소하였다. 또한 naringin은 간조직에서 당신생효소인 glucose-6-phosphatase와 phosphoenolpyruvate carboxykinase 활성도를 감소시킴과 동시에 당이용에 관여하는 glucokinase 활성도와 glycogen 함량을 증가시켰다. 이상의 결과를 종합해 볼 때 naringin은 자연발증 제1형 당뇨동물의 췌장 α-세포와 β-세포를 보호함으로써 혈중 인슐린과 글루카곤 농도를 유지하고 이로써 간조직의 당신생을 억제하고 당이용을 증가시켜 당뇨로 인한 혈당 상승을 억제시키는 것으로 사료된다. 따라서 naringin은 향후 당뇨병 예방 및 개선용 건강기능성식품 및 신약의 소재로 이용될 수 있는 적절한 phytochemical 화합물이라 판단된다.

본 동물실험은 STZ로 유도한 C57BL/6에게 5% sodium butyrate 를 급여했을 때 항당뇨 및 항염증 효과를 연구하고자 하였다. 본 연구에서 STZ로 당뇨를 유발한 마우스에게 5% sodium butyrate를 급여했을 때 체중과 식이섭취량에서는 크게 유의 적 차이가 없음을 확인하였다(p<0.05). STZ에 의한 당뇨 쥐는 인슐린의 분비가 감소되면서 당대사의 불균형을 초래하며 간 등이 비대해진다고 알려져 있으나, 본 연구에서는 간의 장 기 무게에서는 크게 실험군 간에 유의적인 차이가 없었다 (p<0.05). 또한 비장과 흉선의 무게는 0.5% sodium butyrate 첨가 식이군에서 유의적으로 낮아짐을 알 수 있었다(p<0.05). 당뇨병은 염증 상태로서 고혈당으로 인하여 monocyte에서는 여러 염증성 사이토카인이 분비가 활성화된다. TNF-α, IL-6 등은 염증성 사이토카인으로서 혈관염증의 중요한 마커로 인식되고 있고, 당뇨병 환자들은 이러한 염증성 사이토카인 이 높은 수준으로 활성화 된다. STZ 처리 시 마우스 혈청에서 의 염증성 사이토카인의 분비 및 발현이 증가되었으나, 5% sodium butyrate를 급여했을 때 염증성 사이토카인의 분비 및 발현이 저해됨을 확인할 수 있었다. 본 연구는 sodium butyrate 보충은 당뇨병이 유발된 동물모델에서 혈청지질 농도 및 혈 당 조절, 염증 상태를 개선에 다소간의 효과가 있는 것으로 나타났다. 이에 따라 당뇨병과 같은 만성적인 대사질환 개선 에 sodium butyrate가 효과적인 식이인자가 될 것으로 생각된 다. 그러나 앞으로 더 명확한 효능을 탐색하기 위해서 시료 첨가수준의 다각화 및 여러 가지 보완연구가 필요할 것으로 생각 된다.

Anti-diabetic activities of cultured mycelia from Ganoderma applanatum are being evaluated in this study. The OGTT and 4-weeks of repeated oral efficacy tests are conducted in mice at the doses of 0 (vehicle treatment), 25, 75 and 225 ㎎/㎏/day, respectively. In human study, the test article was administered orally every day for 8-week at a dose of 1,500 ㎎/㎏, tid and placebo group. The blood glucose levels (BGL) at 0.5 hour after treatment are significant decreased in all treatment groups of OGTT test. In the 4-week test, BGL of 75 and 225 ㎎/㎏/day group is continuously decreased during all treatment periods and the BGL of 25 ㎎/㎏/day group show decreasing trends at the final week, the pancreas weight of all treatment groups are being increased, and the Langerhans-islet numbers were increased at all treatment groups with a dose-response manner. There are no test article-related abnormal signs and the fasted blood glucose (FBG), postprandial blood glucose (PPG) and HbA1c are decreased significantly after 8-week treatments. These results that the cultured mycelia from Ganoderma applanatum could decrease BGL by protecting the degeneration of Langerhans islets.

Brucellosis is an important bacterial zoonosis in humans and domestic animals. Brucella spp. are taken up, and survive within non-professional and professional phagocytes. In common belief, diabetes mellitus increases susceptibility to pathogenic infection. In this study, Brucella (B.) abortus was inoculated into a diabetic animal model, db/db mice, in order to show the course of brucellosis in diabetic state. The liver proliferation, bacterial burden of the liver, level of cytokines in serum and macrophage migration into liver, were investigated at 14 days post-infection. In comparison with the uninfected control mice, the results revealed that the weight of the liver of infected db/db mice was higher but with lower bacterial load in this organ. The level of MCP-1 mRNA expression in the liver was lower, the levels of IL-12p70, IL-10, TNF-α and IFN-γ in serum was significantly higher and the macrophages migration was significantly lower in infected mice than in the control group. In conclusion, this present study suggested that MCP-1 suppression by B. abortus infection may inhibit the macrophages migration, and consequently may induce to abrogate the bacterial survival in db/db mouse liver. Furthermore, the increased inflammatory cytokines may contribute to inhibition of B. abortus proliferation in diabetic mice.

Periodontal disease induces an increased incidence of tooth loss, particularly in cases with an associated loss of alveolar bone and periodontal ligaments. In this study, alveolar bone loss was detected by micro-computed tomography (CT) following exposure to E. coli lipopolysaccharide (LPS) in a streptozotocin (STZ)-induced diabetic mouse model. A 10 mg/ml dosage of E. coli LPS was applied between the first, second and third molars of the mice three times a week for 10 weeks. The loss of periodontal ligaments and alveolar processes was then evaluated by micro-CT using two and three dimensional microstructure morphometric parameters. In the diabetic mice, E. coli LPS induced the destruction of periodontal ligaments and loss of alveolar process spaces. The distances between periodontal ligaments were significantly widened in the STZ-LPS group compared with the untreated STZ group. The 10 mg/ml exposure to E. coli LPS in the STZ mice also resulted in a significant decrease in the alveolar bone volume fraction. The results of our study suggest that alveolar bone loss can be readily detected by volumetric micro-CT analysis as an increase in the distance between periodontal ligaments and in the alveolar process length.

The goal of this study was to examine the ameliorative effects of black ginseng(BG) in male obese diabetic C57BLKS/ J-db/db mice. Ten-week-old male db/db mice were administrated 300 ㎎/㎏ of F-BG daily for 6 weeks, The db/db mice where corresponded to the normal group and db/db mice which were the diabetic positive group were not provided BG treatment. The supressive effects of treatment were examined on serum lipids levels, which included total cholesterol, triglyceride, LDL-cholesterol and nonesterified fatty acid. Also, weight changes and the relative weight of liver and kidney, organ pathological investigation were measured. The effects of treatment were assessed by comparing the results of the db/db mice that received BG for 6 weeks with that of the diabetic positive group. Significant differences in several biological parameters such as HDL level(p<0.05), TG level(p<0.05) and NEFA level(p<0.05) were observed for the BG group. BG treatment increased the HDL level and decreased the NEFA level, which could ameliorate hyperlipidemia or blood circulation.

Carnosine is a dipeptide (β-alanyl-L-histidine) found in mammalian brain, eye, olfactory bulb and skeletal muscle at high concentrations. Its biological functions include antioxidant and anti-glycation activities. The objectives of this study were to investigate anti-diabetic effects of carnosine as determined by blood glucose levels in glucose tolerance test (GTT) and insulin tolerance test (ITT), insulin level and serum biochemical and lipid levels in male C57BL/6J db/db mice. There were five experimental groups including normal (C57BL/6J), control (vehicle), and three groups of carnosine at doses of 6, 30, and 150 mg/kg b.w. Carnosine was orally administered to the diabetic mice everyday for 8 weeks. There was no significant difference in body weight changes in carnosine-treated groups compared to the control. The treatments of carnosine significantly decreased the blood glucose level in the diabetic mice compared with the control (p < 0.05) after 5 weeks. The treatments of carnosine also significantly decreased the blood glucose levels in GTT and ITT and glycosylated hemoglobin (HbA1c), compared with the control (p < 0.05). Carnosine at the dose of 6 mg/kg significantly decreased the serum insulin level compared to the control (p < 0.05). Carnosine significantly increased total proteins but significantly decreased lactate dehydrogenase and blood urea nitrogen compared with the control (p < 0.05). Carnosine also significantly decreased glucose, LDL, and triglyceride in the serum of diabetic mice compared to the control (p < 0.05). These results suggest that carnosine has a hypoglycermic effect resulting from reduction of glucose and lipid levels and that high carnosine-containing diets or drugs may give a benefit for controlling diabetes mellitus in humans.

Background : Black ginseng is known to be effective product made with ginseng. In general, most black ginseng is manufactured by high teperature condition (90 - 95℃). However this temperature condition may not be optimal to obtain ginsenoside components beneficial for inhibition of diabetes. Here, we examined anti-diabetic effect of black ginseng manufactured by low low temperature process. Methods and Results : For diabetes induction, ICR mice were intraperitoneally injected with alloxan (50 ㎎/㎏). Mice were administered orally with 1 or 3 ㎎/mouse of the extract of black ginseng (BG-L) manufactured with low temperature (80℃), and its anti-diabetic effect was evaluated by measuring the level of glucose in blood. The consecutive administration of BG-L extract resulted in a significant decrease of glucose. In oral and intravenous glucose tolerance test (OGTT and IVGTT, respectively), administration of BG extract significantly reduced the level of glucose in blood within 20 min after glucose treatment. And its suppressive effect on glucose tolerance was effective not only pre-treatment but also post-treatment of BG extract. Oral administration of BG extract enhanced the level of insulin in blood, and decreased the amount of water consumption in alloxan-induced diabetic mice 5 days after alloxan treatment. In addition, BG-L significantly inhibited the level of blood glucose in db/db type-II diabetic mice. Conclusion : These results suggest that the black ginseng extract manufactured manufactured with low temperature (80℃) is a promising candidate applicable to the development of anti-diabetic nutraceutical foods and drugs.

Present study aimed to determine the effect of ‘bitter melon’, a popularly used fruit in Bangladesh and several other Asian countries, on high-fat-diet-induced type 2 diabetes. To investigate the effect, ethanol extract from bitter melon (BME) as a dietary supplement with mouse chow was used. BME was found to significantly attenuate the high-fat diet (HFD) -induced body weight and total fat mass. BME also effectively reduced the insulin resistance induced by the HFD. Furthermore, dietary supplementation of BME was highly effective in increasing insulin sensitivity and reducing hepatic fat and obesity. These results indicate that BME could be effective in attenuating type 2 diabetes and could therefore be a preventive measure against type 2 diabetes.