Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 364180
Title Association of insulin resistance with hyperglycemia in streptozotocin-diabetic pigs - Effects of metformin at isoenergetic feeding in a type 2-like diabetic pig model
Author(s) Koopmans, S.J.; Mroz, Z.; Dekker, R.A.; Corbijn, H.; Ackermans, M.; Sauerwein, H.
Source Metabolism : Clinical and Experimental 55 (2006)7. - ISSN 0026-0495 - p. 960 - 971.
DOI https://doi.org/10.1016/j.metabol.2006.03.004
Department(s) ID - Voeding
Livestock Research
Dierverzorging en Biotechniek
Publication type Refereed Article in a scientific journal
Publication year 2006
Keyword(s) free fatty-acids - glucose-metabolism - lipid-metabolism - miniature pig - food-intake - normal rats - beta-cell - niddm - obesity - pathogenesis
Abstract Insulin-mediated glucose metabolism was investigated in streptozotocin (STZ)¿treated diabetic pigs to explore if the STZ-diabetic pig can be a suitable model for insulin-resistant, type 2 diabetes mellitus. Pigs (40 kg) were meal-fed with a low-fat (5%) diet. Hyperinsulinemic (1, 2, and 8 mU kg¿1 min¿1) clamps and/or 6,6-2H-glucose infusion studies were performed in 36 pigs. Diabetic (slow, 30-minute infusion of 130 mg STZ/kg) vs normal pigs were nonketotic, showed fasting hyperglycemia (21.7 ± 1.1 vs 5.3 ± 0.2 mmol/L), comparable plasma insulin (9 ± 7 vs 5 ± 1 mU/L), and elevated triglyceride concentrations (1.0 ± 0.3 vs 0.2 ± 0.1 mmol/L). After a standard meal, plasma triglycerides, cholesterol, and nonesterified fatty acid concentrations were significantly higher in diabetic vs normal pigs (1.2 ± 0.3 vs 0.3 ± 0.1, 2.3 ± 0.2 vs 1.7 ± 0.1, and 1.5 ± 0.5 vs 0.2 ± 0.1 mmol/L, respectively, P <.05). Fasting whole-body glucose uptake, hepatic glucose production, and urinary glucose excretion were increased (P <.01) in diabetic vs normal pigs (9.1 ± 0.6 vs 4.8 ± 0.4, 11.4 ± 0.6 vs 4.8 ± 0.4, and 2.3 ± 0.2 vs 0.0 ± 0.0 mg kg¿1 min¿1). During hyperinsulinemic euglycemia (6 mmol/L), whole-body glucose uptake was severely reduced (P <.01) and hepatic glucose production was moderately increased (P <.05) in diabetic vs normal pigs (6.7 ± 1.3 vs 21.1 ± 2.2 and 1.7 ± 0.5 vs 0.8 ± 0.3 mg kg¿1 min¿1) despite plasma insulin concentrations of 45 ± 5 vs 24 ± 5 mU/L, respectively. Metformin vs placebo treatment of diabetic pigs (twice 1.5 g/d) for 2 weeks during isoenergetic feeding (1045 kJ/kg body weight0.75) resulted in a reduction in both fasting and postprandial hyperglycemia (14.7 ± 1.5 vs 19.4 ± 0.6 and 24.9 ± 2.2 vs 35.5 ± 4.9 mmol/L), a reduction in daily urinary glucose excretion (250 vs 350 g/kg food), and an increase in insulin-stimulated glucose disposal (9.4 ± 2.2 vs 5.8 ± 1.7 mg kg¿1 min¿1; P <.05), respectively. In conclusion, a slow infusion of STZ (130 mg/kg) in pigs on a low-fat diet induces the characteristic metabolic abnormalities of type 2 diabetes mellitus and its sensitivity to oral metformin therapy. It is therefore a suitable humanoid animal model for studying different aspects of metabolic changes in type 2 diabetes mellitus. Insulin resistance in STZ-diabetic pigs is most likely secondary to hyperglycemia and/or hyperlipidemia and therefore of metabolic origin.
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