Immunohistochemical distribution of glucose‐dependent insulinotropic polypeptide in the adult rat brain

Abstract

We have previously demonstrated that glucose-dependent insulinotropic polypeptide (GIP; gastric inhibitory polypeptide) is present in the adult rat hippocampus. This finding leads to the conclusion that all members of the secretin-glucagon family of gastrointestinal regulatory polypeptides can be found in the brain. To investigate the localization of GIP-producing cells, we used immunohistochemistry on sections of the adult rat brain. High levels of GIP immunoreactivity were observed in the olfactory bulb, hippocampus, and Purkinje cells in the cerebellum. Moreover, a moderate but distinct GIP immunoreactivity was observed in the cerebral cortex, amygdala, substantia nigra, and lateral septal nucleus as well as in several nuclei in the thalamus, hypothalamus, and brainstem. GIP immunoreactivity was frequently found to colocalize with the neuronal marker NeuN but never with the glial marker glial fibrillary acidic protein. Thus, GIP appears to be mainly neuronal to its distribution. This widespread distribution of GIP-immunoreactive cells suggests the involvement of GIP in various neuronal functions and suggests that GIP may act as a neurotransmitter or neuromodulator. This is the first characterization of the anatomical distribution of GIP-immunoreactive cells in the rat brain providing an anatomical framework for future investigations regarding the functions of GIP in the central nervous system.

Glucose-dependent insulinotropic polypeptide receptor knockout mice are impaired in learning, synaptic plasticity, and neurogenesis

“…GIP is synthesized in and secreted from the endocrine K-cells in the intestinal epithelium (Baggio and Drucker 2007;Drucker et al 2006). Recently, GIP and also GIP receptor (GIPR) expression has been reported in the large pyramidal neurons in the cortex and the hippocampus (Nyberg et al 2005(Nyberg et al , 2007. Furthermore, GIP promotes growth, differentiation, proliferation, and survival of ␤-cells (Irwin et al 2006;Trumper et al 2001) and neuronal progenitor cells (Nyberg et al 2005).…”

“…The GIPR is a member of the family of seven-transmembrane domain G protein-coupled receptors (GPCR) (Yip et al 2000). GIP mRNA and GIPR mRNA are expressed in several regions, including the hippocampus, cerebellum, and olfactory system (Nyberg et al 2007;Usdin et al 1993). Activation of GIPR signaling is coupled to increase in cAMP and intracellular Ca 2ϩ levels, as well as activation of phosphatidylinositol 3-kinase (PI-3K), protein kinase A (PKA), protein kinase B (PKB), mitogen-activated protein kinase (MAPK), and phospholipase A 2 (Lu et al 1993;Volz et al 1995).…”

“…Chronic intracerebroventricular infusion of GIP increased the rate of progenitor cell proliferation in the hippocampus of adult rats. In contrast, GIPR knockout (KO) mice displayed a marked decrease in cell proliferation in the dentate gyrus (DG) (Nyberg et al 2005(Nyberg et al , 2007). An increase of apoptosis was also found in the hippocampus of rats immunized against GIP (Tian et al 2010).…”

The Role of Insulin and Incretins in Neuroinflammation and Neurodegeneration

“…The GIP receptor (GIPR) has been detected on neuronal cells, but is yet to be detected on microglia or astrocytes [58,59] . GLP-1 receptors (GLP-1R), on the other hand, are located on neurons [60] , astrocytes [61] and microglia [61] in mice, but in humans have only been confirmed in neurons [62] .…”

Protective Roles of the Incretin Hormones Glucagon-Like Peptide-1 and Glucose-Dependent Insolinotropic Polypeptide Hormones in Neurodegeneration

“…The peptide GIP is also expressed in neurons and serves as a neuronal transmitter (Nyberg et al 2007). Stable analogues such as D-ala 2 -GIP or N-glyc-GIP facilitate synaptic plasticity in the hippocampus, while the antagonist Pro 3 -GIP impairs LTP (V. A. .…”