• 제목/요약/키워드: Insulin Response

검색결과 217건 처리시간 0.028초

Effects of crocin and metformin on methylglyoxal-induced reproductive system dysfunction in diabetic male mice

  • Khorasani, Maryam Kheirollahi;Ahangarpour, Akram;Khorsandi, Layasadat
    • Clinical and Experimental Reproductive Medicine
    • /
    • 제48권3호
    • /
    • pp.221-228
    • /
    • 2021
  • Objective: This study investigated the effect of crocin in methylglyoxal (MGO)-induced diabetic male mice. Methods: Seventy 1-month-old male NMRI mice weighing 20-25 g were divided into seven groups (n=10): sham, MGO (600 mg/kg/day), MGO+crocin (15, 30, and 60 mg/kg/day), MGO+metformin (150 mg/kg/day), and crocin (60 mg/kg/day). MGO was administered orally for 30 days. Starting on day 14, after confirming hyperglycemia, metformin and crocin were administered orally. On day 31, plasma and tissue samples were prepared for experimental assessments. Results: Blood glucose and insulin levels in the MGO group were higher than those in the sham group (p<0.001), and decreased in response to metformin (p<0.001) and crocin treatment (not at all doses). Testis width and volume decreased in the MGO mice and improved in the crocin-treated mice (p<0.05), but not in the metformin group. Superoxide dismutase levels decreased in diabetic mice (p<0.05) and malondialdehyde levels increased (p<0.001). Crocin and metformin improved malondialdehyde and superoxide dismutase. Testosterone (p<0.001) and sperm count (p<0.05) decreased in the diabetic mice, and treatment with metformin and crocin recovered these variables. Luteinizing hormone levels increased in diabetic mice (p<0.001) and crocin treatment (but not metformin) attenuated this increase. Seminiferous diameter and height decreased in the diabetic mice and increased in the treatment groups. Vacuoles and ruptures were seen in diabetic testicular tissue, and crocin improved testicular morphology (p<0.01). Conclusion: MGO increased oxidative stress, reduced sex hormones, and induced histological problems in male reproductive organs. Crocin and metformin improved the reproductive damage caused by MGO-induced diabetes.

Low-dose metronomic doxorubicin inhibits mobilization and differentiation of endothelial progenitor cells through REDD1-mediated VEGFR-2 downregulation

  • Park, Minsik;Kim, Ji Yoon;Kim, Joohwan;Lee, Jeong-Hyung;Kwon, Young-Guen;Kim, Young-Myeong
    • BMB Reports
    • /
    • 제54권9호
    • /
    • pp.470-475
    • /
    • 2021
  • Low-dose metronomic chemotherapy has been introduced as a less toxic and effective strategy to inhibit tumor angiogenesis, but its anti-angiogenic mechanism on endothelial progenitor cells (EPCs) has not been fully elucidated. Here, we investigated the functional role of regulated in development and DNA damage response 1 (REDD1), an endogenous inhibitor of mTORC1, in low-dose doxorubicin (DOX)-mediated dysregulation of EPC functions. DOX treatment induced REDD1 expression in bone marrow mononuclear cells (BMMNCs) and subsequently reduced mTORC1-dependent translation of endothelial growth factor (VEGF) receptor (Vegfr)-2 mRNA, but not that of the mRNA transcripts for Vegfr-1, epidermal growth factor receptor, and insulin-like growth factor-1 receptor. This selective event was a risk factor for the inhibition of BMMNC differentiation into EPCs and their angiogenic responses to VEGF-A, but was not observed in Redd1-deficient BMMNCs. Low-dose metronomic DOX treatment reduced the mobilization of circulating EPCs in B16 melanoma-bearing wild-type but not Redd1-deficient mice. However, REDD1 overexpression inhibited the differentiation and mobilization of EPCs in both wild-type and Redd1-deficient mice. These data suggest that REDD1 is crucial for metronomic DOX-mediated EPC dysfunction through the translational repression of Vegfr-2 transcript, providing REDD1 as a potential therapeutic target for the inhibition of tumor angiogenesis and tumor progression.

Provision of a protein-rich supplement for grazing suckling female beef calves to improve productive performance and metabolic response

  • Moreno, Deilen S;Ortega, Roman M;Marquez, David C;Moreira, Thiago R;Santos, Edson J dos;Almeida, Daniel M de;Paulino, Mario F;Renno, Luciana N;Detmann, Edenio
    • Animal Bioscience
    • /
    • 제35권8호
    • /
    • pp.1174-1183
    • /
    • 2022
  • Objective: This study was conducted to evaluate the effects of the provision of a protein-rich supplement on productive performance, and metabolic profile on grazing suckling female beef calves in tropical conditions during 150 d of experimentation. Methods: Fifty-six Nellore suckling female calves, and their respective dams were distributed in a completely randomised design and made to undergo two treatments as follows: UNS (without supplementation), and SUP (supplementation with 5 g/kg body weight [BW] of a protein supplement). Throughout the experiment, animal performance and metabolic profile were evaluated. Also, ureagenesis and gluconeogenesis were assessed for gene expression. Results: SUP female calves showed a higher voluntary intake (p≤0.03) of the diet components evaluated, digestibility of organic matter (p≤0.02) and microbial nitrogen production (MICN; p≤0.02) compared to UNS female calves. In its turn, serum urea nitrogen (p≤0.01) and insulin-like growth factor-1 (p≤0.03) levels and ureagenesis (p≤0.04) increased in SUP female calves compared to UNS female calves. Blood glucose and triglyceride levels were not affected by supplementation. The average daily gain (ADG) from SUP female calves was higher (p≤0.02) compared with UNS female calves. However, supplementation did not affect the body measures of the animals. Conclusion: In summary, provision of a protein-rich supplement improves the intake and nutrients digestibility, ADG and final BW and increases metabolic indicators of the protein status in grazing suckling female beef calves in tropical conditions.

Ca2+ entry through reverse Na+/Ca2+ exchanger in NCI-H716, glucagon-like peptide-1 secreting cells

  • Choi, Kyung Jin;Hwang, Jin Wook;Kim, Se Hoon;Park, Hyung Seo
    • The Korean Journal of Physiology and Pharmacology
    • /
    • 제26권3호
    • /
    • pp.219-225
    • /
    • 2022
  • Glucagon like peptide-1 (GLP-1) released from enteroendocine L-cells in the intestine has incretin effects due to its ability to amplify glucose-dependent insulin secretion. Promotion of an endogenous release of GLP-1 is one of therapeutic targets for type 2 diabetes mellitus. Although the secretion of GLP-1 in response to nutrient or neural stimuli can be triggered by cytosolic Ca2+ elevation, the stimulus-secretion pathway is not completely understood yet. Therefore, the aim of this study was to investigate the role of reverse Na+/Ca2+ exchanger (rNCX) in Ca2+ entry induced by muscarinic stimulation in NCI-H716 cells, a human enteroendocrine GLP-1 secreting cell line. Intracellular Ca2+ was repetitively oscillated by the perfusion of carbamylcholine (CCh), a muscarinic agonist. The oscillation of cytosolic Ca2+ was ceased by substituting extracellular Na+ with Li+ or NMG+. KB-R7943, a specific rNCX blocker, completely diminished CCh-induced cytosolic Ca2+ oscillation. Type 1 Na+/Ca2+ exchanger (NCX1) proteins were expressed in NCI-H716 cells. These results suggest that rNCX might play a crucial role in Ca2+ entry induced by cholinergic stimulation in NCI-H716 cells, a GLP-1 secreting cell line.

SLC3A2 and SLC7A2 Mediate the Exogenous Putrescine-Induced Adipocyte Differentiation

  • Jin, Eom;Juhyun, Choi;Sung-Suk, Suh;Jong Bae, Seo
    • Molecules and Cells
    • /
    • 제45권12호
    • /
    • pp.963-975
    • /
    • 2022
  • Exogenous polyamines are able to induce life span and improve glucose homeostasis and insulin sensitivity. However, the effects of exogenous polyamines on adipocyte differentiation and which polyamine transporters mediate them have not been elucidated yet. Here, we identified for the first time that exogenous polyamines can clearly stimulate adipocyte differentiation through polyamine transporters, solute carrier family 3 member A2 (SLC3A2) and SLC7A1. Exogenous polyamines markedly promote 3T3-L1 adipocyte differentiation by increasing the intracellular lipid accumulation and the expression of both adipogenic and lipogenic genes in a concentration-dependent manner. In particular, exogenous putrescine mainly regulates adipocyte differentiation in the early and intermediate stages. Moreover, we have assessed the expression of polyamine transporter genes in 3T3-L1 preadipocytes and adipocytes. Interestingly, the putrescine-induced adipocyte differentiation was found to be significantly suppressed in response to a treatment with a polyamine transporter inhibitor (AMXT-1501). Furthermore, knockdown experiments using siRNA that specifically targeted SLC3A2 or SLC7A2, revealed that both SLC3A2 and SLC7A2 act as important transporters in the cellular importing of exogenous putrescine. Thus, the exogenous putrescine entering the adipocytes via cellular transporters is involved in adipogenesis through a modulation of both the mitotic clonal expansion and the expression of master transcription factors. Taken together, these results suggest that exogenous polyamines (such as putrescine) entering the adipocytes through polyamine transporters, can stimulate adipogenesis.

$Ca^{2+}$-induced $Ca^{2+}$ Release from Internal Stores in INS-1 Rat Insulinoma Cells

  • Choi, Kyung-Jin;Cho, Dong-Su;Kim, Ju-Young;Kim, Byung-Joon;Lee, Kyung-Moo;Kim, Shin-Rye;Kim, Dong-Kwan;Kim, Se-Hoon;Park, Hyung-Seo
    • The Korean Journal of Physiology and Pharmacology
    • /
    • 제15권1호
    • /
    • pp.53-59
    • /
    • 2011
  • The secretion of insulin from pancreatic ${\beta}$-cells is triggered by the influx of $Ca^{2+}$ through voltage-dependent $Ca^{2+}$ channels. The resulting elevation of intracellular calcium ($[Ca^{2+}]_i$) triggers additional $Ca^{2+}$ release from internal stores. Less well understood are the mechanisms involved in $Ca^{2+}$ mobilization from internal stores after activation of $Ca^{2+}$ influx. The mobilization process is known as calcium-induced calcium release (CICR). In this study, our goal was to investigate the existence of and the role of caffeine-sensitive ryanodine receptors (RyRs) in a rat pancreatic ${\beta}$-cell line, INS-1 cells. To measure cytosolic and stored $Ca^{2+}$, respectively, cultured INS-1 cells were loaded with fura-2/AM or furaptra/AM. $[Ca^{2+}]_i$ was repetitively increased by caffeine stimulation in normal $Ca^{2+}$ buffer. However, peak $[Ca^{2+}]_i$ was only observed after the first caffeine stimulation in $Ca^{2+}$ free buffer and this increase was markedly blocked by ruthenium red, a RyR blocker. KCl-induced elevations in $[Ca^{2+}]_i$ were reduced by pretreatment with ruthenium red, as well as by depletion of internal $Ca^{2+}$ stores using cyclopiazonic acid (CPA) or caffeine. Caffeine-induced $Ca^{2+}$ mobilization ceased after the internal stores were depleted by carbamylcholine (CCh) or CPA. In permeabilized INS-1 cells,$Ca^{2+}$ release from internal stores was activated by caffeine, $Ca^{2+}$, or ryanodine. Furthermore, ruthenium red completely blocked the CICR response in perrneabilized cells. RyRs were widely distributed throughout the intracellular compartment of INS-1 cells. These results suggest that caffeine-sensitive RyRs exist and modulate the CICR response from internal stores in INS-1 pancreatic ${\beta}$-cells.

운동이 유전자 조절물질에 미치는 영향에 관한 고찰 (A Review : On Exercise Performance Induction Gene Factors Change)

  • 엄기매;양윤권;김태우
    • 대한물리치료과학회지
    • /
    • 제8권1호
    • /
    • pp.745-758
    • /
    • 2001
  • The purpose of study to phenomenological examine and the mechanism regarding the gene(DNA, RNA, Protein) and sports to studied, analyzed. and evaluated. This review considers the evidence for genetic effects in several determinants of endurance performance and resistance performance, namely: body measurements and physique, body fat pulmonary functions, cardiac and circulatory functions, muscle characteristics. substrate utilization, maximal aerobic power and other. Moreover, the response to aerobic training of indicators aerobic work metabolism and endurance performance is reviewed, with emphasis on the specificity of the response and the individual differences observed in training ability. This study indicate that improvement of 'Enhancer Action' in RNA genes changed by exercise or sports. Moreover exercise was effect on Central Dogma with DNA makes RNA makes Protein. and think that occurred with exercise influence on skeletal muscle into cell have to Myosin Heavy Chain (MHC) changed was after exercise performance, which accompanied into skeletal muscle that were exercise-induces gene-modulation that is, take gene mutations. This study known that existed hormone(epinephrine)-immune system with interaction. Exercise were altered insulin binding and MAP Kinase signaling increased into immune cells. This review suggested that the high rate of glutamine utilization by cells of the immune system serves to maintain a high intra cellular concentration of the intermediates of biosynthetic pathways such that optimal rates of DNA, RNA and protein synthesis can be maintained. In the absence of glutamine, lymphocytes do not proliferate in vitro: proliferation increase greatly as the glutamine concentration increase. Glutamine is synthesized in skeletal muscle. Skeletal muscle and plasma glutamine levels are lowered by sepsis, injury, bums, surgery and endurance exercise and in the overtrained athlete. The study of result show that production of ET-1 is markedly increased tissue specifically in the heart by exercise without appreciable changes in endothelin-converting enzyme and endothelial receptor expressions, suggest that myocardial ET-1 may participate in modulation of cardiac function during exercise. Conclusionally, this study indicate that improvement of 'Enhancer Action' in RNA genes changed by exercise or sports. Moreover exercise was effect on Central Dogma with DNA makes RNA makes Protein. This study is expected to contribute the area of sports science, medicine, hereafter more effort is required to establish the relation between gene alters and exercise amount.

  • PDF

Effects of Non-protein Energy Intake on Whole Body Protein Synthesis, Nitrogen Retention and Glucose Turnover in Goats

  • Fujita, Tadahisa;Kajita, Masahiro;Sano, Hiroaki
    • Asian-Australasian Journal of Animal Sciences
    • /
    • 제20권4호
    • /
    • pp.536-542
    • /
    • 2007
  • The responses of whole body protein and glucose kinetics and of nitrogen (N) metabolism to non-protein energy intake (NPEI) were determined using an isotope dilution approach and measurement of N balance in three adult male goats. The diets containing 1.0, 1.5 and 2.0 times ME maintenance requirement, with fixed intake of CP (1.5 times maintenance) and percentage of hay (33%), were fed twice daily for each 21 d experimental period. After an adaptation period of 11 d, N balance was determined over 3 d. On day 17, whole body protein synthesis (WBPS) and glucose irreversible loss rate (ILR) were determined during the absorptive state by a primed-continuous infusion of [$^2H_5$]phenylalanine, [$^2H_2$]tyrosine, [$^2H_4$]tyrosine and [$^{13}C_6$]glucose, with simultaneous measurements of plasma concentrations of metabolites and insulin. Ruminal characteristics were also measured at 6 h after feeding over 3 d. Nitrogen retention tended to increase (p<0.10) with increasing NPEI, although digestible N decreased linearly (p<0.05). Increasing NPEI decreased (p<0.01) ammonia N concentration, but increased acetate (p<0.05) and propionate (p<0.05) concentrations in the rumen. Despite decreased plasma urea N concentration (p<0.01), increased plasma tyrosine concentration (p<0.05), and trends toward increased plasma total amino N (p<0.10) and phenylalanine concentrations (p<0.10) were found in response to increasing NPEI. Increasing NPEI increased ILR of both glucose (p<0.01) and phenylalanine (p<0.05), but did not affect ($p{\geq}0.10$) that of tyrosine. Whole body protein synthesis increased (p<0.05) in response to increasing NPEI, resulting from increased utilization rate for protein synthesis (p<0.05) and unchanged hydroxylation rate of phenylalanine ($p{\geq}0.10$). These results suggest that increasing NPEI may enhance WBPS and glucose turnover at the absorptive state and improve the efficiency of digestible N retention in goats, with possibly decreased ammonia and increased amino acid absorption. In addition, simultaneous increases in WBPS and glucose ILR suggest stimulatory effect of glucose availability on WBPS, especially when sufficient amino acid is supplied.

Effect of Functional Beverage on Weight Control and Body Fat Mass in Overweight Women

  • Chae, Jey-Sook;Lee, Jong-Ho;Koh, Soo-Jeong;Jang, Yong-Soo;Lee, Jin-Hee
    • Biomolecules & Therapeutics
    • /
    • 제11권4호
    • /
    • pp.257-264
    • /
    • 2003
  • Carnitine, hydroxycitric acid, and soy peptide have been known to be anti-obesity agents. The purpose of this study was to evaluate the combined effects of carnitine, hydroxycitric acid, and soy peptide mixture as a potential anti-obesity supplement in overweight women. Overweight premenopausal women (n=33; PIBW>110; 20 to 39 years) were randomized into two groups: the placebo group and the functional beverage group (the test group). Functional beverage was composed of 2000 mg soy peptide, 20 mg L-carnitine and 300 mg garcinia(40% hydroxycitric acid). Body weight and 3 day food dimes, biochemical measurements and computerized tomography were measured at baseline and 8-week. After 8-week consumption of functional beverage with usual diet and exercise, body weight fell an average of 1.4 kg (2.1%). Visceral fat area reduced an average of 7.8% at L1($69.6{\pm}8.7\;vs\;64.2{\pm}7.5\;\textrm{cm}^2$) and 5.1% ($60.7{\pm}4.9\;vs\;57.6{\pm}4.8\;\textrm{cm}^2$, p<0.05) at L4level after weight loss in the test group. Calf fat area in the test group showed about 10% reduction ($31.0{\pm}2.7\;vs=\;27.7{\pm}1.7\;\textrm{cm}^2$, p<0.05) after weight loss. These reductions in fat areas were not shown in the placebo group. There were tendencies of increase in serum levels of $\beta-hydroxybutyrate$, acetoacetate, and total ketones in the test group. There were 7% and 17% insignificant increase in fasting free fatty acid (FFA) and response area of FFA during oral glucose tolerance test(OGTT), respectively, in this group. ill addition, little weight loss in the test group showed 8% but not significant reduction in insulin response area during OGTT. In conclusion, this study shows that taking a mixture of carnitine, hydroxycitric acid, and soy peptide as a potential anti-obesity supplement for 8-week produced advantageous changes in the weight and visceral fat accumulation of overweight women.

천연 암반 심해수 공급이 흰쥐의 면역반응 및 항산화 활성에 미치는 영향 (Effect of the Supply of Natural Water from Deep Sea Rock on the Immune Response and Antioxidant Activity in Rats)

  • 정수진;주은정;유지영;김윤경;조용진;윤병선;조진국;남기택;황성구
    • Journal of Animal Science and Technology
    • /
    • 제48권2호
    • /
    • pp.211-218
    • /
    • 2006
  • 본 연구에서는 천연 암반심해수를 가축 음용수로 개발하고자 2.3% 염분을 함유하고, 칼륨(K), 마그네슘(Mg), 칼슘(Ca), 나트륨(Na), 철(Fe), 망간(Mn), 아연(Zn), 구리(Cu) 등의 광물질을 함유한 암반심해수를 0.5% 및 1%로 희석하여 흰쥐에 공급하며 면역 반응과 항산화 활성에 미치는 영향을 조사하였다. 공시동물로 Sprague Dawley종의 수컷 흰쥐 24마리를 6마리 씩 대조군과 3개의 처리군으로 임의 배치하고, 대조군은 정제수를 급여하였고 처리군은 각각 0.5% 암반심해수, 1% 암반심해수, 지장수를 공급하여 4주 동안 사육하였다. 실험 결과, 1%의 암반수의 경우가 증체량 및 사료섭취량, 사료효율이 우수한 것으로 나타났다. 총음수량은 대조군 보다 0.5% 암반심해수의 경우는 49%, 1% 암반심해수는 22.8%, 지장수는 40.5% 가량 더 많은 것으로 나타났다(p<0.05). 각 조직무게의 경우, 지장수군의 신장주위지방과 정소상체지방은 각각 32%, 25% 적은 것으로 나타났다(p<0.05). B 세포와 T 세포 자극능은 처리군중에서 0.5% 암반심해수 급여군이 가장 높아 대조군보다 44.7%와 207% 증가한 것으로 나타났다(p<0.05). 또 0.5% 암반심해수가 혈청 내 triglyceride는 4%, Free fatty acid는 4%, LDL- cholesterol은 45.9% 감소시키는 등 지질성분 변화에 가장 긍정적인 효과를 나타내었다. 항산화 활성의 경우 TBARS의 양은 0.5% 암반심해수는 21.8%, 1% 암반심해수는 34.7%, 지장수는 20.8% 정도 감소하였다. catalase 활성은 0.5% 암반심해수가 약 2.9배, 지장수가 약 1.6배 증가하였으며, Cu/Zn SOD 활성은 0.5% 암반심해수,가 약 1.5배, 1% 암반심해수가 약 1.7배 ,지장수가 약 1.2배 증가하였으며, MnSOD 활성은 모든 처리군이 대조군에 비해 약간 증가하였다. 이상의 결과로부터 가축에 0.5% 암반심해수의 급여는 LDL 콜레스테롤의 농도가 감소되고, 면역 활성 및 항산화효소 활성이 높아지는 등 고급 축산물생산의 음용수로 유익할 것으로 고찰되었다.