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Insulin inhibits glucose production by a direct effect in diabetic depancreatized dogs during euglycemia
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| Zeitschriftentitel: | American Journal of Physiology-Endocrinology and Metabolism |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , |
| In: | American Journal of Physiology-Endocrinology and Metabolism, 283, 2002, 5, S. E1002-E1007 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Physiological Society
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| Schlagwörter: |
| author_facet |
Gupta, Neehar Sandhu, Harmanjit Goh, Tracy Shah, Keyur Wiesenthal, Stephanie R. Yoshii, Hidenori Chong, Victor Lam, Tony K. T. Haber, C. Andrew Williams, Wendy Tchipashvili, Vaja Giacca, Adria Gupta, Neehar Sandhu, Harmanjit Goh, Tracy Shah, Keyur Wiesenthal, Stephanie R. Yoshii, Hidenori Chong, Victor Lam, Tony K. T. Haber, C. Andrew Williams, Wendy Tchipashvili, Vaja Giacca, Adria |
|---|---|
| author |
Gupta, Neehar Sandhu, Harmanjit Goh, Tracy Shah, Keyur Wiesenthal, Stephanie R. Yoshii, Hidenori Chong, Victor Lam, Tony K. T. Haber, C. Andrew Williams, Wendy Tchipashvili, Vaja Giacca, Adria |
| spellingShingle |
Gupta, Neehar Sandhu, Harmanjit Goh, Tracy Shah, Keyur Wiesenthal, Stephanie R. Yoshii, Hidenori Chong, Victor Lam, Tony K. T. Haber, C. Andrew Williams, Wendy Tchipashvili, Vaja Giacca, Adria American Journal of Physiology-Endocrinology and Metabolism Insulin inhibits glucose production by a direct effect in diabetic depancreatized dogs during euglycemia Physiology (medical) Physiology Endocrinology, Diabetes and Metabolism |
| author_sort |
gupta, neehar |
| spelling |
Gupta, Neehar Sandhu, Harmanjit Goh, Tracy Shah, Keyur Wiesenthal, Stephanie R. Yoshii, Hidenori Chong, Victor Lam, Tony K. T. Haber, C. Andrew Williams, Wendy Tchipashvili, Vaja Giacca, Adria 0193-1849 1522-1555 American Physiological Society Physiology (medical) Physiology Endocrinology, Diabetes and Metabolism http://dx.doi.org/10.1152/ajpendo.00091.2002 <jats:p>In our previous studies in nondiabetic dogs and humans, insulin suppressed glucose production (GP) by both an indirect extrahepatic and a direct hepatic effect. However, insulin had no direct effect on GP in diabetic depancreatized dogs under conditions of moderate hyperglycemia. The present study was designed to investigate whether insulin can inhibit GP by a direct effect in this model under conditions of euglycemia. Depancreatized dogs were made euglycemic (∼6 mmol/l), rather than moderately hyperglycemic (∼10 mmol/l) as in our previous studies, by basal portal insulin infusion. After ∼100 min of euglycemia, a hyperinsulinemic euglycemic clamp was performed by giving an additional infusion of insulin either portally (POR) or peripherally at about one-half the rate (½ PER) to match the peripheral venous insulin concentrations. The greater hepatic insulin load in POR resulted in greater suppression of GP (from 16.5 ± 1.8 to 12.2 ± 1.6 μmol · kg<jats:sup>−1</jats:sup>· min<jats:sup>−1</jats:sup>) than ½ PER (from 17.8 ± 1.9 to 15.6 ± 2.0 μmol · kg<jats:sup>−1</jats:sup>· min<jats:sup>−1</jats:sup>, P < 0.001 vs. POR), consistent with insulin having a direct hepatic effect in suppressing GP. We conclude that the direct effect of insulin to inhibit GP is present in diabetic depancreatized dogs under conditions of acutely induced euglycemia. These results suggest that, in diabetes, the prevailing glycemic level is a determinant of the balance between insulin's direct and indirect effects on GP.</jats:p> Insulin inhibits glucose production by a direct effect in diabetic depancreatized dogs during euglycemia American Journal of Physiology-Endocrinology and Metabolism |
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| title |
Insulin inhibits glucose production by a direct effect in diabetic depancreatized dogs during euglycemia |
| title_unstemmed |
Insulin inhibits glucose production by a direct effect in diabetic depancreatized dogs during euglycemia |
| title_full |
Insulin inhibits glucose production by a direct effect in diabetic depancreatized dogs during euglycemia |
| title_fullStr |
Insulin inhibits glucose production by a direct effect in diabetic depancreatized dogs during euglycemia |
| title_full_unstemmed |
Insulin inhibits glucose production by a direct effect in diabetic depancreatized dogs during euglycemia |
| title_short |
Insulin inhibits glucose production by a direct effect in diabetic depancreatized dogs during euglycemia |
| title_sort |
insulin inhibits glucose production by a direct effect in diabetic depancreatized dogs during euglycemia |
| topic |
Physiology (medical) Physiology Endocrinology, Diabetes and Metabolism |
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http://dx.doi.org/10.1152/ajpendo.00091.2002 |
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2002 |
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E1002-E1007 |
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<jats:p>In our previous studies in nondiabetic dogs and humans, insulin suppressed glucose production (GP) by both an indirect extrahepatic and a direct hepatic effect. However, insulin had no direct effect on GP in diabetic depancreatized dogs under conditions of moderate hyperglycemia. The present study was designed to investigate whether insulin can inhibit GP by a direct effect in this model under conditions of euglycemia. Depancreatized dogs were made euglycemic (∼6 mmol/l), rather than moderately hyperglycemic (∼10 mmol/l) as in our previous studies, by basal portal insulin infusion. After ∼100 min of euglycemia, a hyperinsulinemic euglycemic clamp was performed by giving an additional infusion of insulin either portally (POR) or peripherally at about one-half the rate (½ PER) to match the peripheral venous insulin concentrations. The greater hepatic insulin load in POR resulted in greater suppression of GP (from 16.5 ± 1.8 to 12.2 ± 1.6 μmol · kg<jats:sup>−1</jats:sup>· min<jats:sup>−1</jats:sup>) than ½ PER (from 17.8 ± 1.9 to 15.6 ± 2.0 μmol · kg<jats:sup>−1</jats:sup>· min<jats:sup>−1</jats:sup>, P < 0.001 vs. POR), consistent with insulin having a direct hepatic effect in suppressing GP. We conclude that the direct effect of insulin to inhibit GP is present in diabetic depancreatized dogs under conditions of acutely induced euglycemia. These results suggest that, in diabetes, the prevailing glycemic level is a determinant of the balance between insulin's direct and indirect effects on GP.</jats:p> |
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| author | Gupta, Neehar, Sandhu, Harmanjit, Goh, Tracy, Shah, Keyur, Wiesenthal, Stephanie R., Yoshii, Hidenori, Chong, Victor, Lam, Tony K. T., Haber, C. Andrew, Williams, Wendy, Tchipashvili, Vaja, Giacca, Adria |
| author_facet | Gupta, Neehar, Sandhu, Harmanjit, Goh, Tracy, Shah, Keyur, Wiesenthal, Stephanie R., Yoshii, Hidenori, Chong, Victor, Lam, Tony K. T., Haber, C. Andrew, Williams, Wendy, Tchipashvili, Vaja, Giacca, Adria, Gupta, Neehar, Sandhu, Harmanjit, Goh, Tracy, Shah, Keyur, Wiesenthal, Stephanie R., Yoshii, Hidenori, Chong, Victor, Lam, Tony K. T., Haber, C. Andrew, Williams, Wendy, Tchipashvili, Vaja, Giacca, Adria |
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| description | <jats:p>In our previous studies in nondiabetic dogs and humans, insulin suppressed glucose production (GP) by both an indirect extrahepatic and a direct hepatic effect. However, insulin had no direct effect on GP in diabetic depancreatized dogs under conditions of moderate hyperglycemia. The present study was designed to investigate whether insulin can inhibit GP by a direct effect in this model under conditions of euglycemia. Depancreatized dogs were made euglycemic (∼6 mmol/l), rather than moderately hyperglycemic (∼10 mmol/l) as in our previous studies, by basal portal insulin infusion. After ∼100 min of euglycemia, a hyperinsulinemic euglycemic clamp was performed by giving an additional infusion of insulin either portally (POR) or peripherally at about one-half the rate (½ PER) to match the peripheral venous insulin concentrations. The greater hepatic insulin load in POR resulted in greater suppression of GP (from 16.5 ± 1.8 to 12.2 ± 1.6 μmol · kg<jats:sup>−1</jats:sup>· min<jats:sup>−1</jats:sup>) than ½ PER (from 17.8 ± 1.9 to 15.6 ± 2.0 μmol · kg<jats:sup>−1</jats:sup>· min<jats:sup>−1</jats:sup>, P < 0.001 vs. POR), consistent with insulin having a direct hepatic effect in suppressing GP. We conclude that the direct effect of insulin to inhibit GP is present in diabetic depancreatized dogs under conditions of acutely induced euglycemia. These results suggest that, in diabetes, the prevailing glycemic level is a determinant of the balance between insulin's direct and indirect effects on GP.</jats:p> |
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| spelling | Gupta, Neehar Sandhu, Harmanjit Goh, Tracy Shah, Keyur Wiesenthal, Stephanie R. Yoshii, Hidenori Chong, Victor Lam, Tony K. T. Haber, C. Andrew Williams, Wendy Tchipashvili, Vaja Giacca, Adria 0193-1849 1522-1555 American Physiological Society Physiology (medical) Physiology Endocrinology, Diabetes and Metabolism http://dx.doi.org/10.1152/ajpendo.00091.2002 <jats:p>In our previous studies in nondiabetic dogs and humans, insulin suppressed glucose production (GP) by both an indirect extrahepatic and a direct hepatic effect. However, insulin had no direct effect on GP in diabetic depancreatized dogs under conditions of moderate hyperglycemia. The present study was designed to investigate whether insulin can inhibit GP by a direct effect in this model under conditions of euglycemia. Depancreatized dogs were made euglycemic (∼6 mmol/l), rather than moderately hyperglycemic (∼10 mmol/l) as in our previous studies, by basal portal insulin infusion. After ∼100 min of euglycemia, a hyperinsulinemic euglycemic clamp was performed by giving an additional infusion of insulin either portally (POR) or peripherally at about one-half the rate (½ PER) to match the peripheral venous insulin concentrations. The greater hepatic insulin load in POR resulted in greater suppression of GP (from 16.5 ± 1.8 to 12.2 ± 1.6 μmol · kg<jats:sup>−1</jats:sup>· min<jats:sup>−1</jats:sup>) than ½ PER (from 17.8 ± 1.9 to 15.6 ± 2.0 μmol · kg<jats:sup>−1</jats:sup>· min<jats:sup>−1</jats:sup>, P < 0.001 vs. POR), consistent with insulin having a direct hepatic effect in suppressing GP. We conclude that the direct effect of insulin to inhibit GP is present in diabetic depancreatized dogs under conditions of acutely induced euglycemia. These results suggest that, in diabetes, the prevailing glycemic level is a determinant of the balance between insulin's direct and indirect effects on GP.</jats:p> Insulin inhibits glucose production by a direct effect in diabetic depancreatized dogs during euglycemia American Journal of Physiology-Endocrinology and Metabolism |
| spellingShingle | Gupta, Neehar, Sandhu, Harmanjit, Goh, Tracy, Shah, Keyur, Wiesenthal, Stephanie R., Yoshii, Hidenori, Chong, Victor, Lam, Tony K. T., Haber, C. Andrew, Williams, Wendy, Tchipashvili, Vaja, Giacca, Adria, American Journal of Physiology-Endocrinology and Metabolism, Insulin inhibits glucose production by a direct effect in diabetic depancreatized dogs during euglycemia, Physiology (medical), Physiology, Endocrinology, Diabetes and Metabolism |
| title | Insulin inhibits glucose production by a direct effect in diabetic depancreatized dogs during euglycemia |
| title_full | Insulin inhibits glucose production by a direct effect in diabetic depancreatized dogs during euglycemia |
| title_fullStr | Insulin inhibits glucose production by a direct effect in diabetic depancreatized dogs during euglycemia |
| title_full_unstemmed | Insulin inhibits glucose production by a direct effect in diabetic depancreatized dogs during euglycemia |
| title_short | Insulin inhibits glucose production by a direct effect in diabetic depancreatized dogs during euglycemia |
| title_sort | insulin inhibits glucose production by a direct effect in diabetic depancreatized dogs during euglycemia |
| title_unstemmed | Insulin inhibits glucose production by a direct effect in diabetic depancreatized dogs during euglycemia |
| topic | Physiology (medical), Physiology, Endocrinology, Diabetes and Metabolism |
| url | http://dx.doi.org/10.1152/ajpendo.00091.2002 |