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Ileal Interposition Improves Glucose Tolerance in Low Dose Streptozotocin-treated Diabetic and Euglycemic Rats

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Abstract

Background

The surgical treatment for obesity promotes massive weight loss and early improvement in co-morbid conditions such as type-2 diabetes. Because surgically mediated glycemic improvements are immediate, the mechanisms involved appear to be weight loss independent. Ileal interposition has been used to gain understanding of the relative role that the lower intestine plays in mediating metabolic improvement. Here, we report that ileal interposition is sufficient for improving glucose tolerance in a low-dose streptozotocin-treated diabetic rat model as well as in normal rats with no effect on body weight.

Methods

Male Long–Evans rats were treated with streptozotocin (35 mg/kg) or left untreated and then received sham or ileal interposition. Body weight was measured as well as glucose and insulin tolerance. Plasma insulin and gut hormones were measured during the glucose tolerance test.

Results

Streptozotocin treatment resulted in hyperglycemia within 48 h after treatment. Diabetic rats with ileal interposition showed improvement in glucose tolerance as early as 4 weeks after surgery compared to sham (p < 0.05). By 11 weeks after surgery glucose and insulin tolerance was markedly improved in interposed-diabetic compared to sham-diabetic rats (p < 0.05). Normal non-diabetic rats showed improved glucose tolerance after ileal interposition compared to sham (p < 0.05). Insulin secretion was increased in interposed rats following glucose administration (p < 0.05). The ileal-derived hormones glucagon like peptide-1 (GLP-1), peptide YY (PYY), and glucagon were all significantly elevated in the ileal interposed rats (p < 0.01). Gastric inhibitory polypeptide (GIP) was unchanged. In neither study did body weight between the surgical groups differ at any time point.

Conclusions

Ileal interposition effectively improves glucose tolerance in streptozotocin-diabetic and euglycemic rats. Enhanced insulin secretion can explain the lowered glucose concentrations in euglycemic rats following ileal interposition. Ileal interposition is associated with dramatically elevated ileal hormones, GLP-1, PYY, and glucagon (p < 0.01) with no change in the duodenal hormone GIP.

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Acknowledgement

The present studies were funded in part through a research grant to A.D.S. from the American Society for Metabolic and Bariatric Surgery. We also thank Gitte Koelander Hansen and Vibeke Nielsen for technical assistance, Johannes Josef Fels and Hanne Skov Pedersen for carrying out glucagon analysis and Christian Rosenquist and Susanne Halkier for carrying out total GLP-1 analysis.

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Authors and Affiliations

  1. Department of Physiology, Southern Illinois University School of Medicine, 1135 Lincoln Drive, Carbondale, IL, 62901, USA

    April D. Strader, Sean Z. Goodin & Donna Wendt

  2. GLP-1 and Obesity Biology, Novo Nordisk, Novo Nordisk Park C9.S.29, DK-2760, Maaloev, Denmark

    Trine Ryberg Clausen

Authors
  1. April D. Strader
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  2. Trine Ryberg Clausen
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  3. Sean Z. Goodin
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  4. Donna Wendt
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Correspondence to April D. Strader.

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Strader, A.D., Clausen, T.R., Goodin, S.Z. et al. Ileal Interposition Improves Glucose Tolerance in Low Dose Streptozotocin-treated Diabetic and Euglycemic Rats. OBES SURG 19, 96–104 (2009). https://doi.org/10.1007/s11695-008-9754-x

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  • DOI: https://doi.org/10.1007/s11695-008-9754-x

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