The objective of the research was to identify the presence of adiponectin receptors and to study adiponectin action on glucose uptake and growth in mouse mammary epithelial cells. These cells expressed adiponectin receptors, AdipoR1 and AdipoR2. Insulin (10 ng/ml) or insulin like growth factor-I (IGF-I, 10 ng/ml) alone did not alter the degree of AdipoR1 and AdipoR2 genes expression from 0 to 4 h incubation. Prolactin (10 ng/ml) or epidermal growth factor (EGF, 10 ng/ml) alone also did not induce the two genes’ mRNA in the incubation time. Adiponectin (1 μg/ml) alone or pre-incubation of insulin alone (100 ng/ml) for 2 h prior to adiponectin stimulation did not increase 2-deoxy-D-glucose,[1,2-3H] uptake but adiponectin+pre-incubation of insulin significantly increased glucose uptake compare to control (p<0.05). In a similar way, insulin alone or pre-incubation of adiponectin alone (2 h) did not increase glucose uptake but insulin+pre-incubation of adiponectin increased glucose uptake compare to control (p<0.05). Insulin sensitization for 2 h prior to adiponectin stimulation tended to increase glucose uptake response by the following adiponectin stimulation showing small interaction effect between insulin and adiponectin (p<0.1). However, adiponectin sensitization for 2 hours prior to insulin stimulation did not shown interaction effect between adiponectin and insulin (p>0.1). The glucose uptake by both of hormones seems to be not interactive but additive (p<0.05). Adiponectin in the presence of 2% FBS decreased DNA synthesis of mammary epithelia (p<0.05). AICAR (100 or 200 μM), AMPK activator, decreased mammary epithelial cell growth in the presence of 2% FBS. These results indicate that adiponectin pathway has inhibitory effect on mammary epithelial cell growth.

본 연구는 짚신나물 열수 추출물의 α-glucosidase 저해 활 성을 측정하고, 분화된 근육세포에서 glucose 이용과 인슐린 신호전달에 미치는 영향을 분석하였다. 짚신나물 열수 추출 물(10 ㎎/㎖)은 α-glucosidase 활성을 67% 저해하였으며, 같은 농도의 양성대조구인 acarbose(63%)와 유사한 저해 효과를 보였다. 짚신나물 열수 추출물이 α-glucosidase에 의한 단당 류 생성을 저해함으로 식사 후 혈당이 급격히 상승하는 것을 억제하는데 효과적인 소재로 이용 가능성을 확인하였다. 또한 근육세포에서 인슐린 저항성을 유발하기 위해 지방산(1 mM, palmitic acid)를 처리하였고, glucose의 세포내 유입이 감소 되는 것을 확인하였다. 지방산 처리 세포 모델에서 짚신나 물 열수 추출물(10 ㎍/㎖)은 glucose 이용을 유의적으로 회복 시켜 주었다. Normal 상태의 배양조건에서 근육세포의 포도 당 이용능은 짚신나물 열수 추출물(100 ㎍/㎖) 처리에 의해 유의적으로 증가하였다. 근육세포 내로 glucose 유입은 운반 단백질인 Glut4를 통해 이루어지며, 이것은 인슐린이 신호전 달을 통해 조절한다. 짚신나물 열수 추출물의 세포 내 glucose 이용 증가 효과는 인슐린 신호전달 관련 분자인 Akt 유전자 와 단백질 발현을 증가시킨 것과 관련되는 것으로 추정된다. 결론적으로, 짚신나물 열수 추출물은 소화기관에서의 탄수화 물 흡수 저해와 근육세포 내 glucose 이용 증가를 통해 혈당 조절 및 당 대사 개선에 긍정적인 영향을 미치고 있음을 확인 하였다.

In this study, we observed anti-diabetic effects of acid hydrolyzed silk peptides, where the amount of peptides in the total amino acid mixture was strictly regulated. Using in vitro diabetes models, silk peptide-containing amino acid mixtures of 5.60% (G5), 11.30% (G10), 14.50% (G15), and 20.50% (G20) were examined separately in order to determine whether they have biological activities. According to our results, a cytoprotective effect was observed following treatment of interleukin-1β in RINm5f pancreas β-cells. As a consequence, Bax, a pro-apoptotic gene, was down-regulated, while Bcl-2, a pro-survival gene, was retained at normal level. Results of the 4’,6-diamidino-2-phentylindole (DAPI) staining assay confirmed that G20 has a better cytoprotective effect. Insulin release from RINm5f cells showed a significant increase following treatment with G5-G20, suggesting that silk peptide effectively regulated and induced insulin production. Single treatment with G5-G20 resulted in enhanced glucose uptake in L6 skeletal muscle cells. In addition, a higher amount of each group inhibited the activity of α-glucosidase. In summary, these data suggest that silk peptide may have an anti-diabetic effect through protection of pancreas β-cells and enhancement of insulin release, which showed a close association with Type 1 diabetes mellitus (DM), and can improve glucose uptake, which was the major target for therapy of Type 2 diabetes. Taken together, we concluded that acid hydrolyzed silk peptides can be used effectively for control of blood sugar metabolism via improvement of the problematic indices of Type 1 and Type 2 DM.

Ganoderma lucidum has long been used as a potent medicinal plant. In addition, recent studies showed that G. lucidum is used to prevent or treat various human diseases such as allergy, hepatopathy, hypertension, cancer and diabetes. In this study showed that ethanol extract from G. lucidum have potential inhibitory effects of glycerol 3-phosphat acyltransferase (GPAT) activity and increase of glucose uptake on skeletal muscle cells. Inhibition of GPAT, which catalyze the first step in de novo TAG synthesis, has been proposed as one of the drug targets for insulin resistance and type-2 diabetes. G. lucidum extract inhibited GPAT activity. Bioassay-guided fractionation and isolation of bio-active substances from ethanol extracts of G. lucidum were carried out by using chromatographic techniques and in vitro GPAT enzyme assay. One of bioactive molecules, ergosterol peroxide, was isolated and identified by physical and spectral properties. In this study showed that ethanol extract from G. lucidum and ergosterol peroxide have potential anti- diabetes effects through the increase of glucose uptake. This was as sociated with increased activity AMP-activated protein kinase(AMPK). AMPK is another regulatory protein in the glucose uptake pathway and energy metabolism. The result was that the increase of glucose uptake by G. lucidum extract might be mediated by AMPK.

인슐린 저항성이 발생된 흰쥐 골격근에서 n-3 다불포화지방산이 당수송에 어떤 영향을 미치는지 연구한 본 논문을 요약하면 다음과 같다. 5주간의 식이에 의한 각군간의 유의한 체중 변화는 없었다. 5주간의 고지방식이에 의하여 혈당은 정상식이군의 83mg/dl에 비하여 94mg/dl로 13% 더 증가하였다(p<0.05). n-3 다불포화지방산에 의하여서는 혈당의 유의적 감소는 없었으나 다소 감소하였다. 혈장 인슐린은 정상식이군의 11.6U/ml에 비하여 고지방식이군은 32.4U/ml로 높았으며(p<0.01), n-3 다불포화지방산에 의하여 28.7U/ml로 감소하였다(p<0.01). 가자미근의 당수송은 시험관 실험에서 고지방식이군이 정상식이군에 비하여 기초상태 뿐만아니라 인슐린 1, 10, 100nM에서도 현저히 감소하여(p<0.01) 인슐린 감수성과 반응도 모두 감소한 인슐린 저항성을 보여 주었다. 고지방식이군에 n-3 다불포화지방산의 첨가시 고지방식이군에 비하여 기초상태, 인슐린 1, 10, 100nM에서 유의하게(p<0.01) 증가하였으나 정상군의 그것에는 미치지 못하였다. 이상의 결과로 미루어 보아 5주간의 고지방식이시 당수송에 장애와 골격근의 인슐린 저항성이 발견되었으며, 고지방식이에 n-3 다불포화지방산의 첨가에 의해서 골격근 인슐린 저항성의 정도가 억제되므로 고지방식이에 의한 인슐린 저항성은 n-3 다불포화지방산이 효과적으로 예방이 가능할 것으로 생각되었다.

Obesity is characterized by a state of chronic low-grade inflammation and insulin resistance, which are aggravated by the interaction between hypertrophic adipocytes and macrophages. In this study, we investigated the effects of tangeretin on inflammatory changes and glucose uptake in a coculture of hypertrophic adipocytes and macrophages. Tangeretin decreased nitric oxide production and the expression of interleukin (IL)-6, IL-1β, tumor necrosis factor-α, inducible nitric oxide synthase, and cyclooxygenase-2 in a coculture of 3T3-L1 adipocytes and RAW 264.7 cells. Tangeretin also increased glucose uptake in the coculture system, but did not affect the phosphorylation of insulin receptor substrate (IRS) and Akt. These results suggest that tangeretin improves insulin resistance by attenuating obesity-induced inflammation in adipose tissue.