Diabetes & Metabolism Journal

Original Articles

Relation of Absolute or Relative Adiposity to Insulin Resistance, Retinol Binding Protein-4, Leptin, and Adiponectin in Type 2 Diabetes: You Lim Kim, Tae Kyun Kim, Eun Sun Cheong, Dong Geum Shin, Gyu Sik Choi, Jihye Jung, Kyung-Ah Han, Kyung Wan Min; Diabetes Metab J. 2012;36(6):415-421. Published online December 12, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.6.415

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Background

Central fat mass (CFM) correlates with insulin resistance and increases the risk of type 2 diabetes and cardiovascular complications; however, peripheral fat mass (PFM) is associated with insulin sensitivity. The aim of this study was to investigate the relation of absolute and relative regional adiposity to insulin resistance index and adipokines in type 2 diabetes.

Methods

Total of 83 overweighted-Korean women with type 2 diabetes were enrolled, and rate constants for plasma glucose disappearance (K_ITT) and serum adipokines, such as retinol binding protein-4 (RBP4), leptin, and adiponectin, were measured. Using dual X-ray absorptiometry, trunk fat mass (in kilograms) was defined as CFM, sum of fat mass on the lower extremities (in kilograms) as PFM, and sum of CFM and PFM as total fat mass (TFM). PFM/TFM ratio, CFM/TFM ratio, and PFM/CFM ratio were defined as relative adiposity.

Results

Median age was 55.9 years, mean body mass index 27.2 kg/m², and mean HbA1c level 7.12±0.84%. K_ITT was positively associated with PMF/TFM ratio, PMF/CFM ratio, and negatively with CFM/TFM ratio, but was not associated with TFM, PFM, or CFM. RBP4 levels also had a significant relationship with PMF/TFM ratio and PMF/CFM ratio. Adiponectin, leptin, and apolipoprotein A levels were related to absolute adiposity, while only adiponectin to relative adiposity. In correlation analysis, K_ITT in type 2 diabetes was positively related with HbA1c, fasting glucose, RBP4, and free fatty acid.

Conclusion

These results suggest that increased relative amount of peripheral fat mass may aggravate insulin resistance in type 2 diabetes.

Citations

Citations to this article as recorded by

Retinol-binding protein-4 and nonalcoholic fatty liver disease
Hangkai Huang, Chengfu Xu
Chinese Medical Journal.2022; 135(10): 1182. CrossRef
MANF in POMC Neurons Promotes Brown Adipose Tissue Thermogenesis and Protects Against Diet-Induced Obesity
Qin Tang, Qinhui Liu, Jiahui Li, Jiamin Yan, Xiandan Jing, Jinhang Zhang, Yan Xia, Ying Xu, Yanping Li, Jinhan He
Diabetes.2022; 71(11): 2344. CrossRef
The relation between body fat distribution, plasma concentrations of adipokines and the metabolic syndrome in patients with clinically manifest vascular disease
Ilse M Schrover, Yolanda van der Graaf, Wilko Spiering, Frank LJ Visseren
European Journal of Preventive Cardiology.2018; 25(14): 1548. CrossRef
Visceral Fat Mass Has Stronger Associations with Diabetes and Prediabetes than Other Anthropometric Obesity Indicators among Korean Adults
Suk Hwa Jung, Kyoung Hwa Ha, Dae Jung Kim
Yonsei Medical Journal.2016; 57(3): 674. CrossRef
Adipokines, cytokines and body fat stores in hepatitis C virus liver steatosis
Emilio González-Reimers
World Journal of Hepatology.2016; 8(1): 74. CrossRef
The effect of resveratrol on the expression of AdipoR1 in kidneys of diabetic nephropathy
Hongfei Ji, Lina Wu, Xiaokun Ma, Xiaojun Ma, Guijun Qin
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Retinol-binding protein 4 and insulin resistance are related to body fat in primary and secondary schoolchildren: the Ouro Preto study
Ana Paula Pereira Castro, Ana Paula Carlos Cândido, Roney Luiz de Carvalho Nicolato, Ivo Santana Caldas, George Luiz Lins Machado-Coelho
European Journal of Nutrition.2014; 53(2): 433. CrossRef
The Effects of Marathon Running on Retinol Binding Protein 4 and C-reactive Protein Levels in Healthy Middle-aged Korean Men
Jisuk Chae, Sungmin Kim, Junga Lee, Justin Y. Jeon
The Korean Journal of Obesity.2014; 23(3): 203. CrossRef
Modeling metabolic homeostasis and nutrient sensing in Drosophila: implications for aging and metabolic diseases
Edward Owusu-Ansah, Norbert Perrimon
Disease Models & Mechanisms.2014; 7(3): 343. CrossRef
Beneficial Effects of Fresh and Fermented Kimchi in Prediabetic Individuals
So-Yeon An, Min Suk Lee, Ja Young Jeon, Eun Suk Ha, Tae Ho Kim, Ja Young Yoon, Chang-Ok Ok, Hye-Kyoung Lee, Won-Sun Hwang, Sun Jung Choe, Seung Jin Han, Hae Jin Kim, Dae Jung Kim, Kwan-Woo Lee
Annals of Nutrition and Metabolism.2013; 63(1-2): 111. CrossRef
Regional Adiposity, Adipokines, and Insulin Resistance in Type 2 Diabetes
Jee-Young Oh
Diabetes & Metabolism Journal.2012; 36(6): 412. CrossRef

The Effects of Glyburide on Apoptosis and Endoplasmic Reticulum Stress in INS-1 Cells in a Glucolipotoxic Condition: Min Jeong Kwon, Hye Suk Chung, Chang Shin Yoon, Jung Hae Ko, Hae Jung Jun, Tae Kyun Kim, Soon Hee Lee, Kyung Soo Ko, Byoung Doo Rhee, Mi Kyung Kim, Jeong Hyun Park; Diabetes Metab J. 2011;35(5):480-488. Published online October 31, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.5.480

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Abstract PDF PubReader

Background

β-cell death due to endoplasmic reticulum (ER) stress has been regarded as an important pathogenic component of type 2 diabetes. The possibility has been suggested that sulfonylurea, currently being used as one of the main oral hypoglycemic agents of type 2 diabetes, increases ER stress, which could lead to sulfonylurea failure. The authors of the present study examined ER stress of β-cells in a glucolipotoxic condition using glyburide (GB) in an environment mimicking type 2 diabetes.

Methods

Apoptosis was induced by adding various concentrations of GB (0.001 to 200 µM) to a glucolipotoxic condition using 33 mM glucose, and the effects of varied concentrations of palmitate were evaluated via annexin V staining. The markers of ER stress and pro-apoptotic markers were assessed by Western blotting and semi-quantitative reverse transcription-polymerase chain reaction. Additionally, the anti-apoptotic markers were evaluated.

Results

Addition of any concentration of GB in 150 µM palmitate and 33 mM glucose did not increase apoptosis. The expression of phosphorylated eukaryotic initiation factor (eIF-2α) was increased and cleaved caspase 3 was decreased by adding GB to a glucolipotoxic condition. However, other ER stress-associated markers such as Bip-1, X-box binding protein-1, ATF-4 and C/EBP-homologous protein transcription factor and anti-apoptotic markers phosphor-p85 phosphatidylinositol 3-kinase and phosphorylation of Akt did not change significantly.

Conclusion

GB did not show further deleterious effects on the degree of apoptosis or ER stress of INS-1 cells in a glucolipotoxic condition. Increased phosphorylation of eIF-2α may attenuate ER stress for adaptation to increased ER protein load.

Citations

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Expression profiles of stress-related genes in islets from donors with progressively impaired glucose metabolism
Marcus Lundberg, Anton Stenwall, Angie Tegehall, Olle Korsgren, Oskar Skog
Islets.2018; 10(2): 69. CrossRef
Pharmacological Modulators of Endoplasmic Reticulum Stress in Metabolic Diseases
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International Journal of Molecular Sciences.2016; 17(2): 192. CrossRef
The TRPA1 channel and oral hypoglycemic agents
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Dimethyl sulfoxide reduces hepatocellular lipid accumulation through autophagy induction
Young Mi Song, Sun-Ok Song, Yong-Keun Jung, Eun-Seok Kang, Bong Soo Cha, Hyun Chul Lee, Byung-Wan Lee
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The Duration of Sulfonylurea Treatment Is Associated withβ-Cell Dysfunction in Patients with Type 2 Diabetes Mellitus
Mi-Seon Shin, Jee Hee Yu, Chang Hee Jung, Jenie Yoonoo Hwang, Woo Je Lee, Min-Seon Kim, Joong-Yeol Park
Diabetes Technology & Therapeutics.2012; 14(11): 1033. CrossRef

Bone Mineral Density in Prediabetic Men: Ju Hee Lee, Yun Hyeong Lee, Kyoung Hye Jung, Min Kyeong Kim, Hye Won Jang, Tae Kyun Kim, Hyun Jin Kim, Young Suk Jo, Minho Shong, Tae Yong Lee, Bon Jeong Ku; Korean Diabetes J. 2010;34(5):294-302. Published online October 31, 2010; DOI: https://doi.org/10.4093/kdj.2010.34.5.294

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Abstract PDF PubReader

Background

There are many studies regarding the effects of insulin on bone metabolism and changes in bone mineral density (BMD) in the setting of diabetes. The effect of prediabetes on BMD is not known.

Methods

A total of 802 men participated in the Korea Rural Genomic Cohort Study (in Geumsan County). According to the results of an oral glucose tolerance test, subjects were classified into normal, prediabetic, and diabetic categories. One hundred twenty-four subjects diagnosed with type 2 diabetes were excluded, leaving 678 subjects for the study inclusion. BMD was estimated with a quantitative ultrasonometer.

Results

The average BMD T scores of normal and prediabetic subjects were -1.34 ± 1.42 and -1.33 ± 1.30, respectively; there was no significant difference in the BMD T scores between these groups. The BMD T score was inversely associated with age and positively correlated with body weight, body mass index, total cholesterol, low density lipoprotein cholesterol, and HbA1c. On multiple linear regression analysis, low density lipoprotein cholesterol was the only statistically significant variable for prediabetes (β = 0.007, P = 0.005). On the stepwise regression analysis, age (β = -0.026, P < 0.001), the body mass index (β = 0.079, P < 0.001), and low density lipoprotein cholesterol (β = 0.004, P = 0.016) were significant variables for prediabetes.

Conclusions

There was no significant difference in the BMD T score between the normal and prediabetic subjects. Further studies are needed regarding the association of fracture risk and changes in BMD with the development of overt diabetes.

Citations

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More Rapid Bone Mineral Density Loss in Older Men With Diabetes: The Osteoporotic Fractures in Men (MrOS) Study
Flavia Tramontana, Nicola Napoli, Stephanie Litwack-Harrison, Douglas C Bauer, Eric S Orwoll, Jane A Cauley, Elsa S Strotmeyer, Ann V Schwartz
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Prediabetes and skeletal health
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Osteoporosis in Men with Diabetes Mellitus
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Response: Bone Mineral Density in Prediabetic Men (Korean Diabetes J 2010;34:294-302)
Ju Hee Lee, Hyun Jin Kim, Bon Jeong Ku
Korean Diabetes Journal.2010; 34(6): 386. CrossRef
Letter: Bone Mineral Density in Prediabetic Men (Korean Diabetes J 2010;34:294-302)
Chul-Hee Kim
Korean Diabetes Journal.2010; 34(6): 384. CrossRef

The Effect of Glucose Fluctuation on Apoptosis and Function of INS-1 Pancreatic Beta Cells: Mi Kyung Kim, Hye Sook Jung, Chang Shin Yoon, Jung Hae Ko, Hae Jung Jun, Tae Kyun Kim, Min Jeong Kwon, Soon Hee Lee, Kyung Soo Ko, Byoung Doo Rhee, Jeong Hyun Park; Korean Diabetes J. 2010;34(1):47-54. Published online February 28, 2010; DOI: https://doi.org/10.4093/kdj.2010.34.1.47

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Background

Blood glucose level continuously fluctuates within a certain range in the human body. In diabetes patients, the extent of such fluctuation is large, despite the strict control of blood glucose. Blood glucose fluctuation has been shown to mediate more adverse effects on vascular endothelial cells and diabetes complications than chronic hyperglycemia, which has been explained as due to oxidative stress. As few previous studies have reported the effects of chronic and intermittent hyperglycemia on the apoptosis and function of pancreatic beta cells, this study reported herein was performed to investigate such effects on these cells.

Methods

For chronic hyperglycemia, INS-1 cells were cultured for 5 days with changes of RPMI 1640 medium containing 33 mM glucose every 12 hours. For intermittent hyperglycemia, the medium containing 11 mM glucose was exchanged with the medium containing 33 mM glucose every 12 hours. Apoptosis was assessed by TUNEL assay Hoechst staining and cleaved caspase 3. Insulin secretory capacity was assessed, and the expression of Mn-SOD and Bcl-2 was measured by Western blotting.

Results

In comparison to the control group, INS-1 cells exposed to chronic hyperglycemia and intermittent hyperglycemia showed an increase in apoptosis. The apoptosis of INS-1 cells exposed to intermittent hyperglycemia increased significantly more than the apoptosis of INS-1 cells exposed to chronic hyperglycemia. In comparison to the control group, the insulin secretory capacity in the two hyperglycemic states was decreased, and more with intermittent hyperglycemia than with chronic hyperglycemia. The expression of Mn-SOD and Bcl-2 increased more with chronic hyperglycemia than with intermittent hyperglycemia.

Conclusion

Intermittent hyperglycemia induced a higher degree of apoptosis and decreased the insulin secretory capacity more in pancreatic beta cells than chronic hyperglycemia. This activity may be mediated by the anti-oxidative enzyme Mn-SOD and the anti-apoptotic signal Bcl-2.

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