Circulating ApoJ is closely associated with insulin resistance in human subjects

Ji A Seo, Min Cheol Kang, Theodore P. Ciaraldi, Sang Soo Kim, Kyong Soo Park, Charles Choe, Won Min Hwang, Dong Mee Lim, Olivia Farr, Christos Mantzoros, Robert R. Henry, Young Bum Kim

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Objective Insulin resistance is a major risk factor for type 2 diabetes. ApolipoproteinJ (ApoJ) has been implicated in altered pathophysiologic states including cardiovascular and Alzheimer's disease. However, the function of ApoJ in regulation of glucose homeostasis remains unclear. This study sought to determine whether serum ApoJ levels are associated with insulin resistance in human subjects and if they change after interventions that improve insulin sensitivity. Methods Serum ApoJ levels and insulin resistance status were assessed in nondiabetic (ND) and type 2 diabetic (T2D) subjects. The impacts of rosiglitazone or metformin therapy on serum ApoJ levels and glucose disposal rate (GDR) during a hyperinsulinemic/euglycemic clamp were evaluated in a separate cohort of T2D subjects. Total ApoJ protein or that associated with the HDL and LDL fractions was measured by immunoblotting or ELISA. Results Fasting serum ApoJ levels were greatly elevated in T2D subjects (ND vs T2D; 100 ± 8.3 vs. 150.6 ± 8.5 AU, P < 0.0001). Circulating ApoJ levels strongly correlated with fasting glucose, fasting insulin, HOMA-IR, and BMI. ApoJ levels were significantly and independently associated with HOMA-IR, even after adjustment for age, sex, and BMI. Rosiglitazone treatment in T2D subjects resulted in a reduction in serum ApoJ levels (before vs. after treatment; 100 ± 13.9 vs. 77 ± 15.2 AU, P = 0.015), whereas metformin had no effect on ApoJ levels. The change in ApoJ levels during treatment was inversely associated with the change in GDR. Interestingly, ApoJ content in the LDL fraction was inversely associated with HOMA-IR. Conclusion Serum ApoJ levels are closely correlated with the magnitude of insulin resistance regardless of obesity, and decrease along with improvement of insulin resistance in response only to rosiglitazone in type 2 diabetes.

Original languageEnglish
Pages (from-to)155-166
Number of pages12
JournalMetabolism: Clinical and Experimental
Volume78
DOIs
Publication statusPublished - 2018 Jan 1

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rosiglitazone
Insulin Resistance
Serum
Glucose
Fasting
Metformin
Type 2 Diabetes Mellitus
Glucose Clamp Technique
Therapeutics
Immunoblotting
Alzheimer Disease
Homeostasis
Cardiovascular Diseases
Obesity
Enzyme-Linked Immunosorbent Assay
Insulin
Proteins

Keywords

  • Apolipoprotein J
  • Insulin resistance
  • Type 2 diabetes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Circulating ApoJ is closely associated with insulin resistance in human subjects. / Seo, Ji A; Kang, Min Cheol; Ciaraldi, Theodore P.; Kim, Sang Soo; Park, Kyong Soo; Choe, Charles; Hwang, Won Min; Lim, Dong Mee; Farr, Olivia; Mantzoros, Christos; Henry, Robert R.; Kim, Young Bum.

In: Metabolism: Clinical and Experimental, Vol. 78, 01.01.2018, p. 155-166.

Research output: Contribution to journalArticle

Seo, JA, Kang, MC, Ciaraldi, TP, Kim, SS, Park, KS, Choe, C, Hwang, WM, Lim, DM, Farr, O, Mantzoros, C, Henry, RR & Kim, YB 2018, 'Circulating ApoJ is closely associated with insulin resistance in human subjects', Metabolism: Clinical and Experimental, vol. 78, pp. 155-166. https://doi.org/10.1016/j.metabol.2017.09.014
Seo, Ji A ; Kang, Min Cheol ; Ciaraldi, Theodore P. ; Kim, Sang Soo ; Park, Kyong Soo ; Choe, Charles ; Hwang, Won Min ; Lim, Dong Mee ; Farr, Olivia ; Mantzoros, Christos ; Henry, Robert R. ; Kim, Young Bum. / Circulating ApoJ is closely associated with insulin resistance in human subjects. In: Metabolism: Clinical and Experimental. 2018 ; Vol. 78. pp. 155-166.
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abstract = "Objective Insulin resistance is a major risk factor for type 2 diabetes. ApolipoproteinJ (ApoJ) has been implicated in altered pathophysiologic states including cardiovascular and Alzheimer's disease. However, the function of ApoJ in regulation of glucose homeostasis remains unclear. This study sought to determine whether serum ApoJ levels are associated with insulin resistance in human subjects and if they change after interventions that improve insulin sensitivity. Methods Serum ApoJ levels and insulin resistance status were assessed in nondiabetic (ND) and type 2 diabetic (T2D) subjects. The impacts of rosiglitazone or metformin therapy on serum ApoJ levels and glucose disposal rate (GDR) during a hyperinsulinemic/euglycemic clamp were evaluated in a separate cohort of T2D subjects. Total ApoJ protein or that associated with the HDL and LDL fractions was measured by immunoblotting or ELISA. Results Fasting serum ApoJ levels were greatly elevated in T2D subjects (ND vs T2D; 100 ± 8.3 vs. 150.6 ± 8.5 AU, P < 0.0001). Circulating ApoJ levels strongly correlated with fasting glucose, fasting insulin, HOMA-IR, and BMI. ApoJ levels were significantly and independently associated with HOMA-IR, even after adjustment for age, sex, and BMI. Rosiglitazone treatment in T2D subjects resulted in a reduction in serum ApoJ levels (before vs. after treatment; 100 ± 13.9 vs. 77 ± 15.2 AU, P = 0.015), whereas metformin had no effect on ApoJ levels. The change in ApoJ levels during treatment was inversely associated with the change in GDR. Interestingly, ApoJ content in the LDL fraction was inversely associated with HOMA-IR. Conclusion Serum ApoJ levels are closely correlated with the magnitude of insulin resistance regardless of obesity, and decrease along with improvement of insulin resistance in response only to rosiglitazone in type 2 diabetes.",
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T1 - Circulating ApoJ is closely associated with insulin resistance in human subjects

AU - Seo, Ji A

AU - Kang, Min Cheol

AU - Ciaraldi, Theodore P.

AU - Kim, Sang Soo

AU - Park, Kyong Soo

AU - Choe, Charles

AU - Hwang, Won Min

AU - Lim, Dong Mee

AU - Farr, Olivia

AU - Mantzoros, Christos

AU - Henry, Robert R.

AU - Kim, Young Bum

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Objective Insulin resistance is a major risk factor for type 2 diabetes. ApolipoproteinJ (ApoJ) has been implicated in altered pathophysiologic states including cardiovascular and Alzheimer's disease. However, the function of ApoJ in regulation of glucose homeostasis remains unclear. This study sought to determine whether serum ApoJ levels are associated with insulin resistance in human subjects and if they change after interventions that improve insulin sensitivity. Methods Serum ApoJ levels and insulin resistance status were assessed in nondiabetic (ND) and type 2 diabetic (T2D) subjects. The impacts of rosiglitazone or metformin therapy on serum ApoJ levels and glucose disposal rate (GDR) during a hyperinsulinemic/euglycemic clamp were evaluated in a separate cohort of T2D subjects. Total ApoJ protein or that associated with the HDL and LDL fractions was measured by immunoblotting or ELISA. Results Fasting serum ApoJ levels were greatly elevated in T2D subjects (ND vs T2D; 100 ± 8.3 vs. 150.6 ± 8.5 AU, P < 0.0001). Circulating ApoJ levels strongly correlated with fasting glucose, fasting insulin, HOMA-IR, and BMI. ApoJ levels were significantly and independently associated with HOMA-IR, even after adjustment for age, sex, and BMI. Rosiglitazone treatment in T2D subjects resulted in a reduction in serum ApoJ levels (before vs. after treatment; 100 ± 13.9 vs. 77 ± 15.2 AU, P = 0.015), whereas metformin had no effect on ApoJ levels. The change in ApoJ levels during treatment was inversely associated with the change in GDR. Interestingly, ApoJ content in the LDL fraction was inversely associated with HOMA-IR. Conclusion Serum ApoJ levels are closely correlated with the magnitude of insulin resistance regardless of obesity, and decrease along with improvement of insulin resistance in response only to rosiglitazone in type 2 diabetes.

AB - Objective Insulin resistance is a major risk factor for type 2 diabetes. ApolipoproteinJ (ApoJ) has been implicated in altered pathophysiologic states including cardiovascular and Alzheimer's disease. However, the function of ApoJ in regulation of glucose homeostasis remains unclear. This study sought to determine whether serum ApoJ levels are associated with insulin resistance in human subjects and if they change after interventions that improve insulin sensitivity. Methods Serum ApoJ levels and insulin resistance status were assessed in nondiabetic (ND) and type 2 diabetic (T2D) subjects. The impacts of rosiglitazone or metformin therapy on serum ApoJ levels and glucose disposal rate (GDR) during a hyperinsulinemic/euglycemic clamp were evaluated in a separate cohort of T2D subjects. Total ApoJ protein or that associated with the HDL and LDL fractions was measured by immunoblotting or ELISA. Results Fasting serum ApoJ levels were greatly elevated in T2D subjects (ND vs T2D; 100 ± 8.3 vs. 150.6 ± 8.5 AU, P < 0.0001). Circulating ApoJ levels strongly correlated with fasting glucose, fasting insulin, HOMA-IR, and BMI. ApoJ levels were significantly and independently associated with HOMA-IR, even after adjustment for age, sex, and BMI. Rosiglitazone treatment in T2D subjects resulted in a reduction in serum ApoJ levels (before vs. after treatment; 100 ± 13.9 vs. 77 ± 15.2 AU, P = 0.015), whereas metformin had no effect on ApoJ levels. The change in ApoJ levels during treatment was inversely associated with the change in GDR. Interestingly, ApoJ content in the LDL fraction was inversely associated with HOMA-IR. Conclusion Serum ApoJ levels are closely correlated with the magnitude of insulin resistance regardless of obesity, and decrease along with improvement of insulin resistance in response only to rosiglitazone in type 2 diabetes.

KW - Apolipoprotein J

KW - Insulin resistance

KW - Type 2 diabetes

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