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Gene & Protein in Disease                                             β-cell regeneration and stem cell niche



            may be used to modify pathways, such as manipulating   messengers. However, fura-2-based fluorescence imaging
            Wnt signaling, p21, and homeobox protein Hox-B4. 58  revealed calcium signals within intact pancreatic islets
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              Membrane  proteins  known  as  GPCRs  can  detect  a   when arginine vasopressin or ghrelin was applied.  The
            wide range of signals, including photons, ions, proteins,   methodology enabled the measurement of intracellular
            neurotransmitters, and hormones. The GPCR superfamily   cyclic adenosine monophosphate (cAMP) levels caused by
            is divided into five subfamilies: glutamate, frizzled/taste2,   receptors linked to Gs and Gi/o proteins, allowing for an
                                                               accurate assessment of GPCR activity in intact islets. The
            rhodopsin, adhesion, and secretin receptors. Abnormalities   second messengers IP1, cAMP, and calcium can be detected,
            in ligand concentration, GPCR protein expression, or
            mutations are implicated in numerous pathophysiological   thus enhancing our understanding of their diverse effects
            conditions, including diseases of the gastrointestinal   on cellular function. Continuous investigation into ligand-
            system, central nervous system, respiratory system,   receptor interactions, conformational analyses, effector-
            musculoskeletal pathologies, cardiovascular and metabolic   receptor engagement, and signaling patterns should lead
            systems, immune diseases, and eye disorders. GPCRs   to new approaches for developing novel therapeutics.
            account for 30% of all recognized pharmacological targets,   The G protein-coupled estrogen receptor (GPER) and its
                                                               potential involvement in illness development and disease
            making them central to the development of innovative   treatment are currently under research. GPER binding
            drugs and a common therapeutic intervention strategy.    mediates a number of activities, including metabolic flaws
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            However, a significant challenge persists: integrating   and insulin resistance, as suggested by in vivo research.
            extrinsic and intrinsic regulatory fate determinants through
            the main signaling channels into cohesive networks of   The treatment of T2D and obesity often involves the
            regulatory systems.  This understanding could lead to   use of glucagon-like peptide-1 receptor (GLP-1R) agonists,
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            novel methods for preserving and boosting HSCs in vitro.   which enhance pancreatic cell activity and increase insulin
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            Interestingly, the molecular mechanisms for managing and   sensitivity by promoting weight loss.  These agonists are
            maintaining plant stem cells show similarities to those in   synthetic analogs of naturally occurring agonists such as
            animals.                                           GLP-1(7-36) NH  or its paralogue exendin-4, modified
                                                                             2
                                                               to possess longer pharmacokinetic half-lives. Current
              Furthermore, this section covers the most recent
            research on the genetic control of signaling in plant   research has demonstrated that altering the amino acid
                                                               sequence of orthosteric GLP-1R peptide agonists can
            meristems. It begins with providing guidance on the   significantly change their intracellular signaling profiles,
            regulation of the shoot and root apical meristems. The   resulting in decreased coupling to intracellular effectors.
            borders  between  plant  stem  cells  and  their  developing   This imbalance, favoring G protein-dependent signaling,
            progeny are maintained through transcriptional and   is frequently referred to as “bias.” In the initial stages
            posttranscriptional regulation. A  graphic representation   of diabetes, there is a disruption in the initial phase of
            of the roles of signaling molecules, such as the hormones   insulin production, followed by a gradual decline in
            auxin and cytokines, is provided (Figure  10). Another   the glucose’s capacity to stimulate insulin secretion. To
            aspect of control is documented in lateral meristems, where   develop therapeutic interventions aimed at altering insulin
            numerous crucial regulators of stem cell maintenance   secretory activity and/or cell mass, a better knowledge
            show unexpected parallels to those in apical meristems.   of the signaling pathways associated with the activation
            The regulation of grass rhizomes is also discussed, as many   of GPCRs and their interactions within cells is essential.
            agricultural plants fall into this category. The reproductive   Gi-GPCRs, with interact with G proteins of the i/o class,
            success of these plants, and consequently their agronomic   play a role in regulating a variety of cellular activities
            yield, depends greatly on shoot architecture. Therefore,   in mammalian tissues, but their influence on tissue
            topics such as phyllotaxy, leaf initiation patterning, and   development and expansion is less apparent.  This article
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            floral induction are covered, given their importance for   covers recent findings on GPCRs functionally expressed
            members of the grass family.  A brief presentation on the   in  β-cells, which have important properties for the
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            relevant genetic and hormonal regulation is presented.  development of T2D therapies. While pancreatic islet cells
              The study investigated second messenger activation in   express GPCRs, their specific roles remain unclear. A study
            mouse pancreatic islets, which regulate glucose-induced   identified specific GPCRs, such as free fatty acid receptor 4
            insulin release. It was found that activating Gq/11-coupled   (FFAR4), prostaglandin E receptor 4 (PTGER4), purinergic
            receptors in primary cells increased second messenger   receptor (P2RY14), adrenoceptor beta 2 (ADRB2), and
            IP1, but this signal was eliminated when a Gq/11 protein   G-protein coupled receptor 54 (GPR54, also identified
            inhibitor was used. Activation of V1 vasopressin and   as KISS1R), located in primary cilia of both mouse and
            ghrelin receptors did not significantly increase second   human islet cells.  These GPCRs stimulate ciliary cAMP
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            Volume 3 Issue 2 (2024)                         13                              doi: 10.36922/gpd.2996
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