Positive feedback loops are inherently unstable systems. For example, an increase in the concentration of a substance causes feedback that ultimately causes the concentration of the substance to decrease. negative feedback loops, in which a change in a given direction causes change in the opposite direction.For example, an increase in the concentration of a substance causes feedback that produces continued increases in concentration. positive feedback loops, in which a change in a given direction causes additional change in the same direction.Typically, we divide feedback loops into two main types: Effectors make adjustments to the variable. The control center compares this value against a reference value (set point). The receptor senses the change in the variable. An initiation event or stimulus causes a change in a variable. Feedbackįeedback is a situation when the output or response of a loop impacts or influences the input or stimulus. When a stimulus, or change in the environment, is present, feedback loops respond to keep systems functioning near a set point, or ideal level. Remember that homeostasis is the maintenance of a relatively stable internal environment. Chapter 9: The Lymphatic System and Immunityĥ3. Endocrine Homeostasis and Integration of Systemsĥ9. Introduction to the Respiratory Systemħ0. Reproductive Structures and Functions Chapter 3: Homeostasis and Feedback LoopsĢ3. Introduction to the Integumentary SystemĢ4. Integumentary Structures and Functionsģ9. Nervous System Levels of OrganizationĤ2. Cardiovascular Structures and FunctionsĤ3. Cardiovascular Levels of OrganizationĤ5. Cardiovascular Integration of Systems Chapter 2 Part 4: Higher Order Structuresġ8. Organ Systems, The Whole Body, and Populations Chapter 2 Part 1: Levels of Organization - Introductionġ5. Cell Division and Control of Cell Number Chapter 1: Introduction to Anatomy and Physiology The novel role of the Dyn/KOR axis in islet function in healthy and diabetogenic conditions can have profound implications for glucose homeostasis and serve to develop potential targets for T2D.I. We demonstrate that the β- to δ-cell Dyn/KOR negative feedback loop is upregulated in diabetes and pharmacological inhibition or genetic deletion of KOR in δ-cells improves glucose homeostasis in high-fat diet (HFD)-fed mice, demonstrating the therapeutic potential of this system. Remarkably, dynorphin mRNA is one of the top ten most upregulated genes in islets from HFD-fed mice, higher than several critical β-cell genes, including pdx1 or ucn3. Our data also show that Dyn is increased in islets from HFD-fed mice (8-fold) and in human β-cells from T2D donors. Using perifusion and static incubation studies, we show that Dyn induces SST secretion and decreases insulin secretion in mouse and human islets and that Dyn fails to induce SST secretion in islets from mice with KOR deletion in δ-cells, thereby providing a mechanism for feedback control of insulin secretion (β- to δ-cell Dyn/KOR negative feedback loop). Dyn acts mainly through the k-opioid receptor (KOR) expressed in all islet cells with the highest expression in δ-cells. Dyn, an opioid peptide involved in stress response, pain, and addiction is synthesized in human and mouse β-cells and secreted in response to glucose. Here, we show that intra-islet dynorphin (Dyn) stimulates somatostatin (SST) secretion and is a novel factor regulating islet function and insulin secretion in human and mouse islets. Therefore, understanding intra-islet communication is imperative for developing new strategies for diabetes management. The dysregulation of these signals contributes to impaired glucose homeostasis and diabetes. Within the pancreatic islet, the crosstalk between different islet cells through paracrine signals orchestrates a hormonal response that controls glucose levels.
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