Glucose‐dependent insulinotropic polypeptide (GIP) and its receptor (GIPR): Cellular localization, lesion‐affected expression, and impaired regenerative axonal growth

Abstract

Glucose-dependent insulinotropic polypeptide (GIP) was initially described to be rapidly regulated by endocrine cells in response to nutrient ingestion, with stimulatory effects on insulin synthesis and release. Previously, we demonstrated a significant up-regulation of GIP mRNA in the rat subiculum after fornix injury. To gain more insight into the lesion-induced expression of GIP and its receptor (GIPR), expression profiles of the mRNAs were studied after rat sciatic nerve crush injury in 1) affected lumbar dorsal root ganglia (DRG), 2) spinal cord segments, and 3) proximal and distal nerve fragments by means of quantitative RT-PCR. Our results clearly identified lesion-induced as well as tissue type-specific mRNA regulation of GIP and its receptor. Furthermore, comprehensive immunohistochemical stainings not only confirmed and exceeded the previous observation of neuronal GIP expression but also revealed corresponding GIPR expression, implying putative modulatory functions of GIP/GIPR signaling in adult neurons. In complement, we also observed expression of GIP and its receptor in myelinating Schwann cells and oligodendrocytes. Polarized localization of GIPR in the abaxonal Schwann cell membranes, plasma membrane-associated GIPR expression of satellite cells, and ependymal GIPR expression strongly suggests complex cell type-specific functions of GIP and GIPR in the adult nervous system that are presumably mediated by autocrine and paracrine interactions, respectively. Notably, in vivo analyses with GIPR-deficient mice suggest a critical role of GIP/GIPR signal transduction in promoting spontaneous recovery after nerve crush, insofar as traumatic injury of GIPR-deficient mouse sciatic nerve revealed impaired axonal regeneration compared with wild-type mice.

Lateral Allosterism in the Glucagon Receptor Family: Glucagon-Like Peptide 1 Induces G-Protein-Coupled Receptor Heteromer Formation

“…), is shown. pression has been reported for various cell types of the central and peripheral nervous systems and was linked to endocrine or paracrine signaling (Buhren et al, 2009). Half of the GLP-1 produced in the intestine is metabolized to GLP-1(9 -36) as it enters the circulation (Hansen et al, 1999), which makes this antagonist the predominant bioavailable form of GLP-1.…”

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

“…Others have also reported that GIP increased progenitor cell proliferation both in vivo and in vitro (Nyberg et al 2005;Tian et al 2010). GIP also promotes axonal growth after nerve crush (Buhren et al 2009), indicating that GIP has growth factor-like properties that can be of use in neuroprotection and neuroregeneration. We also tested the number of immature neurons as identified by DCX, a cell marker for immature neurons , to test whether the lack of progenitor cells in the GIPR KO mice leads to a reduction in young neurons.…”

“…Furthermore, GIP has been shown to promote axonal regeneration after sciatic nerve injury. GIPRdeficient mice were associated with impaired spontaneous nerve regeneration compared with the normal mice (Buhren et al 2009).…”

Neuroprotective effects of glucose-dependent insulinotropic polypeptide in Alzheimer’s disease

“…Notably, in vivo analyses with GIPRdeficient mice suggest a critical role of GIP/GIPR signal transduction in promoting spontaneous recovery after nerve crush, insofar as traumatic injury of GIPR-deficient mouse sciatic nerve revealed impaired axonal regeneration compared with wild-type mice (Buhren et al, 2009).…”