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The p75 neurotrophin receptor is required for the major loss of sympathetic nerves from islets under autoimmune attack.

Taborsky GJ, Mei Q, Bornfeldt KE, Hackney DJ, Mundinger TO - Diabetes (2014)

Bottom Line: Similar nerve loss, chemically induced, was sufficient to impair sympathetically mediated glucagon secretion.We conclude that an inducible autoimmune attack of the islet causes a marked and islet-selective loss of sympathetic nerves that precedes islet collapse and hyperglycemia.The p75NTR mediates this nerve loss but plays no role in mediating the loss of islet β-cells or the subsequent diabetes. p75NTR-mediated nerve loss may contribute to the impaired glucose counterregulation seen in type 1 diabetes.

View Article: PubMed Central - PubMed

Affiliation: Division of Endocrinology/Metabolism, Veterans Affairs Puget Sound Health Care System, Seattle, WADivision of Endocrinology, Metabolism and Nutrition, Department of Medicine, University of Washington, Seattle, WA taborsky@u.washington.edu.

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Loss of islet sympathetic nerves is associated with T-lymphocytic infiltration. Loss of NPY nerves (arrows) from an islet of an Ins2-GPTg mouse 7 (E), but not 4 (C), days after LCMV injection compared with no LCMV control (A). CD3 staining revealing T-lymphocytic infiltration of an islet of an Ins2-GPTg mouse 7 (F), but not 4 (D), days after LCMV injection compared with no LCMV control (B). Quantification of the islet area occupied by CD3-positive T-lymphocytes (G) or NPY-positive nerves (H) before and 4 and 7 days after LCMV injection. *Significant difference (P < 0.0005) compared with no LCMV control.
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Figure 2: Loss of islet sympathetic nerves is associated with T-lymphocytic infiltration. Loss of NPY nerves (arrows) from an islet of an Ins2-GPTg mouse 7 (E), but not 4 (C), days after LCMV injection compared with no LCMV control (A). CD3 staining revealing T-lymphocytic infiltration of an islet of an Ins2-GPTg mouse 7 (F), but not 4 (D), days after LCMV injection compared with no LCMV control (B). Quantification of the islet area occupied by CD3-positive T-lymphocytes (G) or NPY-positive nerves (H) before and 4 and 7 days after LCMV injection. *Significant difference (P < 0.0005) compared with no LCMV control.

Mentions: Because the onset of diabetes was so precise in LCMV-injected Ins2-GPTg mice, we were next able to determine if islet sympathetic nerves were lost during the autoimmune attack of the islet that precedes the development of diabetic hyperglycemia. Therefore, we examined islet sympathetic nerves before and 4 and 7 days after LCMV injection. Four days after LCMV injection, the sympathetic innervation of the islet appeared normal (Fig. 2C and H). However, 7 days after LCMV injection, there was a marked loss (Δ = −59%; P = 0.0002) of islet sympathetic nerves (n = 8; Fig. 2E and H) compared with noninjected, age-matched (10-week) controls (n = 7; Fig. 2A and H). Islet area in 7-day LCMV-injected mice (35,960 ± 3,526 μm2) was not significantly different from noninjected mice (29,800 ± 1,120 μm2).


The p75 neurotrophin receptor is required for the major loss of sympathetic nerves from islets under autoimmune attack.

Taborsky GJ, Mei Q, Bornfeldt KE, Hackney DJ, Mundinger TO - Diabetes (2014)

Loss of islet sympathetic nerves is associated with T-lymphocytic infiltration. Loss of NPY nerves (arrows) from an islet of an Ins2-GPTg mouse 7 (E), but not 4 (C), days after LCMV injection compared with no LCMV control (A). CD3 staining revealing T-lymphocytic infiltration of an islet of an Ins2-GPTg mouse 7 (F), but not 4 (D), days after LCMV injection compared with no LCMV control (B). Quantification of the islet area occupied by CD3-positive T-lymphocytes (G) or NPY-positive nerves (H) before and 4 and 7 days after LCMV injection. *Significant difference (P < 0.0005) compared with no LCMV control.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4066345&req=5

Figure 2: Loss of islet sympathetic nerves is associated with T-lymphocytic infiltration. Loss of NPY nerves (arrows) from an islet of an Ins2-GPTg mouse 7 (E), but not 4 (C), days after LCMV injection compared with no LCMV control (A). CD3 staining revealing T-lymphocytic infiltration of an islet of an Ins2-GPTg mouse 7 (F), but not 4 (D), days after LCMV injection compared with no LCMV control (B). Quantification of the islet area occupied by CD3-positive T-lymphocytes (G) or NPY-positive nerves (H) before and 4 and 7 days after LCMV injection. *Significant difference (P < 0.0005) compared with no LCMV control.
Mentions: Because the onset of diabetes was so precise in LCMV-injected Ins2-GPTg mice, we were next able to determine if islet sympathetic nerves were lost during the autoimmune attack of the islet that precedes the development of diabetic hyperglycemia. Therefore, we examined islet sympathetic nerves before and 4 and 7 days after LCMV injection. Four days after LCMV injection, the sympathetic innervation of the islet appeared normal (Fig. 2C and H). However, 7 days after LCMV injection, there was a marked loss (Δ = −59%; P = 0.0002) of islet sympathetic nerves (n = 8; Fig. 2E and H) compared with noninjected, age-matched (10-week) controls (n = 7; Fig. 2A and H). Islet area in 7-day LCMV-injected mice (35,960 ± 3,526 μm2) was not significantly different from noninjected mice (29,800 ± 1,120 μm2).

Bottom Line: Similar nerve loss, chemically induced, was sufficient to impair sympathetically mediated glucagon secretion.We conclude that an inducible autoimmune attack of the islet causes a marked and islet-selective loss of sympathetic nerves that precedes islet collapse and hyperglycemia.The p75NTR mediates this nerve loss but plays no role in mediating the loss of islet β-cells or the subsequent diabetes. p75NTR-mediated nerve loss may contribute to the impaired glucose counterregulation seen in type 1 diabetes.

View Article: PubMed Central - PubMed

Affiliation: Division of Endocrinology/Metabolism, Veterans Affairs Puget Sound Health Care System, Seattle, WADivision of Endocrinology, Metabolism and Nutrition, Department of Medicine, University of Washington, Seattle, WA taborsky@u.washington.edu.

Show MeSH
Related in: MedlinePlus