The Hypothalamic Arcuate Nucleus–Median Eminence Is a Target for Sustained Diabetes Remission Induced by Fibroblast Growth Factor 1

• DOI: 10.2337/db19-0025
• Publication Date: 2019-02-22T21:45:12Z
• Authors: Jenny M. Brown; Jarrad M. Scarlett; Miles E. Matsen; Hong T. Nguyen; Anna Secher; Rasmus Jorgensen; Gregory J. Morton; Michael W. Schwartz
• Keywords: Median eminence; FGF1

In rodent models of type 2 diabetes (T2D), sustained remission diabetic hyperglycemia can be induced by a single intracerebroventricular (icv) injection fibroblast growth factor 1 (FGF1). To identify the brain areas responsible for this effect, we first used immunohistochemistry to map hypothalamic distribution phosphorylated extracellular signal–related kinase 1/2 (pERK1/2), marker mitogen-activated protein kinase–ERK signal transduction downstream FGF receptor activation. Twenty minutes after icv FGF1 in adult male Wistar rats, pERK1/2 staining was detected primarily two areas: arcuate nucleus–median eminence (ARC-ME) and paraventricular nucleus (PVN). determine whether an action localized either ARC-ME or PVN is capable mimicking antidiabetic effect elicited FGF1, microinjected saline vehicle low dose (0.3 µg/side) bilaterally into area Zucker Diabetic Fatty model T2D, monitored daily food intake, body weight, blood glucose levels over 3-week period. Whereas bilateral intra-arcuate microinjection without lasting >3 weeks observed following ARC-ME. This cannot attributed leakage cerebrospinal fluid subsequent on other areas, since same total effect. Combined with our finding that glycemia parameters, conclude (but not PVN) target FGF1.