Insulin Resistance Develops Due to an Imbalance in the Synthesis of Cyclic AMP and the Natural Cyclic AMP Antagonist Prostaglandylinositol Cyclic Phosphate (Cyclic PIP)
The reasons initiating insulin resistance are not identified. Various metabolic derailments have been characterized. These are the outcome and not the initiation of insulin resistance. In animal models of type 2 diabetes and hypertension, a decreased hormonal stimulation of the synthesis of the cycl...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | Stresses |
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| Online Access: | https://www.mdpi.com/2673-7140/3/4/52 |
| _version_ | 1797379284972601344 |
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| author | Heinrich K. Wasner |
| author_facet | Heinrich K. Wasner |
| author_sort | Heinrich K. Wasner |
| collection | DOAJ |
| description | The reasons initiating insulin resistance are not identified. Various metabolic derailments have been characterized. These are the outcome and not the initiation of insulin resistance. In animal models of type 2 diabetes and hypertension, a decreased hormonal stimulation of the synthesis of the cyclic AMP antagonist prostaglandylinositol cyclic phosphate (cyclic PIP) was determined. The resultant imbalance of the action of cyclic AMP and cyclic PIP shifts metabolic regulation to the dominance of catabolism and a decrease in imperative anabolism. This dominance develops gradually since the more cyclic AMP dominates, the more the synthesis of cyclic PIP will be inhibited. Vanishing actions of cyclic PIP are its 10-fold activation of glucose uptake in adipocytes, its inhibition of insulin release from pancreatic β-cells, its inhibition of PKA and its 7-fold activation of protein ser/thr phosphatase. Reduced synthesis of cyclic PIP results from (a) decreased substrate availability, (b) long-time elevated cyclic AMP levels resulting from stress overloads and (c) aging and the gradual decrease in the synthesis of hormones which likely maintain mechanisms that stimulate cyclic PIP synthesis. The need is to discover which hormones, such as growth hormone, insulin-like growth factor-1, dehydroepiandrosterone, and testosterone, are involved in maintaining the stimulation of cyclic PIP synthesis. |
| first_indexed | 2024-03-08T20:20:57Z |
| format | Article |
| id | doaj.art-55fd831961b041b19a7380fedf39126c |
| institution | Directory Open Access Journal |
| issn | 2673-7140 |
| language | English |
| last_indexed | 2024-03-08T20:20:57Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Stresses |
| spelling | doaj.art-55fd831961b041b19a7380fedf39126c2023-12-22T14:43:23ZengMDPI AGStresses2673-71402023-11-013476277210.3390/stresses3040052Insulin Resistance Develops Due to an Imbalance in the Synthesis of Cyclic AMP and the Natural Cyclic AMP Antagonist Prostaglandylinositol Cyclic Phosphate (Cyclic PIP)Heinrich K. Wasner0BioReg Biopharm, Technology Innovation Laboratory, University of Illinois at Chicago, Chicago, IL 60612, USAThe reasons initiating insulin resistance are not identified. Various metabolic derailments have been characterized. These are the outcome and not the initiation of insulin resistance. In animal models of type 2 diabetes and hypertension, a decreased hormonal stimulation of the synthesis of the cyclic AMP antagonist prostaglandylinositol cyclic phosphate (cyclic PIP) was determined. The resultant imbalance of the action of cyclic AMP and cyclic PIP shifts metabolic regulation to the dominance of catabolism and a decrease in imperative anabolism. This dominance develops gradually since the more cyclic AMP dominates, the more the synthesis of cyclic PIP will be inhibited. Vanishing actions of cyclic PIP are its 10-fold activation of glucose uptake in adipocytes, its inhibition of insulin release from pancreatic β-cells, its inhibition of PKA and its 7-fold activation of protein ser/thr phosphatase. Reduced synthesis of cyclic PIP results from (a) decreased substrate availability, (b) long-time elevated cyclic AMP levels resulting from stress overloads and (c) aging and the gradual decrease in the synthesis of hormones which likely maintain mechanisms that stimulate cyclic PIP synthesis. The need is to discover which hormones, such as growth hormone, insulin-like growth factor-1, dehydroepiandrosterone, and testosterone, are involved in maintaining the stimulation of cyclic PIP synthesis.https://www.mdpi.com/2673-7140/3/4/52cyclic AMPcyclic PIPinsulin resistanceprostaglandylinositol cyclic phosphateprotein phosphorylationprotein kinase A |
| spellingShingle | Heinrich K. Wasner Insulin Resistance Develops Due to an Imbalance in the Synthesis of Cyclic AMP and the Natural Cyclic AMP Antagonist Prostaglandylinositol Cyclic Phosphate (Cyclic PIP) Stresses cyclic AMP cyclic PIP insulin resistance prostaglandylinositol cyclic phosphate protein phosphorylation protein kinase A |
| title | Insulin Resistance Develops Due to an Imbalance in the Synthesis of Cyclic AMP and the Natural Cyclic AMP Antagonist Prostaglandylinositol Cyclic Phosphate (Cyclic PIP) |
| title_full | Insulin Resistance Develops Due to an Imbalance in the Synthesis of Cyclic AMP and the Natural Cyclic AMP Antagonist Prostaglandylinositol Cyclic Phosphate (Cyclic PIP) |
| title_fullStr | Insulin Resistance Develops Due to an Imbalance in the Synthesis of Cyclic AMP and the Natural Cyclic AMP Antagonist Prostaglandylinositol Cyclic Phosphate (Cyclic PIP) |
| title_full_unstemmed | Insulin Resistance Develops Due to an Imbalance in the Synthesis of Cyclic AMP and the Natural Cyclic AMP Antagonist Prostaglandylinositol Cyclic Phosphate (Cyclic PIP) |
| title_short | Insulin Resistance Develops Due to an Imbalance in the Synthesis of Cyclic AMP and the Natural Cyclic AMP Antagonist Prostaglandylinositol Cyclic Phosphate (Cyclic PIP) |
| title_sort | insulin resistance develops due to an imbalance in the synthesis of cyclic amp and the natural cyclic amp antagonist prostaglandylinositol cyclic phosphate cyclic pip |
| topic | cyclic AMP cyclic PIP insulin resistance prostaglandylinositol cyclic phosphate protein phosphorylation protein kinase A |
| url | https://www.mdpi.com/2673-7140/3/4/52 |
| work_keys_str_mv | AT heinrichkwasner insulinresistancedevelopsduetoanimbalanceinthesynthesisofcyclicampandthenaturalcyclicampantagonistprostaglandylinositolcyclicphosphatecyclicpip |