{"id":2578,"date":"2025-08-21T13:21:45","date_gmt":"2025-08-21T13:21:45","guid":{"rendered":"https:\/\/pjthornalley.com\/?page_id=2578"},"modified":"2026-03-22T10:17:52","modified_gmt":"2026-03-22T10:17:52","slug":"news","status":"publish","type":"page","link":"https:\/\/pjthornalley.com\/index.php\/news\/","title":{"rendered":"NEWS"},"content":{"rendered":"\n

Hi! This is my news feed. I will be adding posts to this feed for your interest. Kind regards, Paul<\/p>\n\n\n\n

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GlucoRegulate vs Tirzepatide in obesity<\/h2>\n\n\n\n

Dietary supplements are often taken to support good health. It’s rare to see evidence of comparison with leading pharmaceuticals in clinical trial. An example is weight loss drug Tirzepatide<\/strong> (Zepbound<\/strong>) and supplement GlucoRegulate<\/strong>. Tirzepatide (5 mg, once weekly subcutaneous injection) for 72 weeks to subjects living with obesity improved insulin sensitivity, measured by the oral glucose insulin sensitivity (OGIS) index, by 75 units – including diet counselling to achieve 500 calories per day decrease and at least 150 min per week exercise; SURMOUNT-1 trial. Dietary supplement GlucoRegulate (once daily, oral capsule) for 8 weeks to subjects living with obesity improved OGIS index by 58 units – with no change in diet and exercise; HATFF trial. A similar improvement in metabolic health with GlucoRegulate as for Tirzepatide and achieved over a shorter period with minimal lifestyle change and low cost to consumer and healthcare provider. A remarkable comparison indeed!<\/strong> Increased insulin sensitivity in obesity is important to counter insulin resistance for improved metabolic, heart, liver, kidney and respiratory health. GlucoRegulate is a supplement by GloVitality (UK) Ltd <\/strong>(https:\/\/glovitality.com\/glucoregulate\/<\/a>).<\/p>\n\n\n\n

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Supporting papers: Mounjaro – Mari et al., Diabetes Care 2025; 48: 1622\u20131627; GlucoRegulate (then called Glo1 inducer) – Xue at al., Diabetes 2016; 65: 2282\u20132294.<\/p>\n\n\n\n

Paul J Thornalley 19th March 2026<\/p>\n\n\n\n

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Insulin resistance<\/h2>\n\n\n\n

Insulin resistance is the impaired response to insulin of tissues that are normally insulin-responsive. It is increasingly recognized as impacting the liver, skeletal muscle, adipose tissue and also the brain. The mechanisms are distinct in different tissues. It is prevalent in obesity, prediabetes and type 2 diabetes and is often the primary initiator leading to type 2 diabetes development. <\/p>\n\n\n\n

Hepatic insulin resistance<\/strong> is so-called “mixed” insulin resistance and is due to down regulation of insulin receptor substrate 2 (IRS-2). A major consequence of this is impaired down regulation of gluconeogenesis in the post-meal absorptive phase leading to hypersecretion of glucose from the liver. It is caused by overactivation of carbohydrate-response element binding protein (ChREBP) by a sugar rich diet, hyperinsulinaemia and also multilayered epigenetic and extrahepatic mechanisms, including regulation by the central nervous system and glucagon. Involvement of ChREBP is driven by glucokinase-linked glycolytic overload in hepatocytes. It is likely reversed by GlucoRegulate<\/strong> supplement, trans-resveratrol with hesperetin (Rabbani and Thornalley, Clinical Science 139, 1 \u2013 25, 2025).<\/p>\n\n\n\n

Peripheral insulin resistance <\/strong>is the impaired response of skeletal muscle and adipose tissue to insulin. Normally in the absorptive phase insulin stimulates uptake of glucose into muscle for glycogen synthesis and uptake of glucose into adipose tissue for synthesis of lipids. Impaired recruitment of insulin-dependent GLUT4 glucose transporter appears to have a key role. We have described how hexokinase-2 linked glycolytic overload in the fasting period during impaired fasting glucose with increased fasting glucose concentration contributes to this. It is corrected by GlucoRegulate<\/strong> supplement (Rabbani and Thornalley, Front. Endocrinol. 14: 1268308, 2024).<\/p>\n\n\n\n

Brain insulin resistance<\/strong> may be inferred from decreased response amplitudes to auditory and visual stimuli using electroencephalography and magneto-encephalography during a hyperinsulinemic euglycemic clamp. It is typically found in subjects living with obesity and type 2 diabetes which also have hepatic and peripheral insulin resistance. It is associated with decreased memory and improved cognitive performance and is thought to be mediated by inflammation and oxidative stress (Milstein, J.L., and Ferris, H.A. Mol Metab 52<\/em>, 101234, 2021). It is likely corrected by GlucoRegulat<\/strong>e supplement which is currently under consideration.<\/p>\n\n\n\n

Paul J Thornalley, 15th March 2026<\/p>\n\n\n\n

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Happy New Year 2026<\/h2>\n\n\n
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Happy New Year! Looking forward to working with in-house and collaborating international teams in 2026 to advance projects in biomedical research and commercialization – particularly of precision dietary\/food supplement GlucoRegulate (through Glovitality Ltd<\/a> and Glocentrica Ltd<\/a>) and screening blood test for autism (through iDiagnostix Ltd<\/a>).<\/p>\n\n\n\n

\u201cCome, my friends, \u2018Tis not too late to seek a newer world<\/em>\u201d. From Ulysses, Alfred Lord Tennyson. <\/p>\n\n\n\n

Paul J Thornalley, 1st January 2026<\/p>\n\n\n\n

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What have we discovered in 2025?<\/h2>\n\n\n\n
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  1. Diets rich in simple sugars and\/or fats provide a gateway to metabolic dysfunction associated steatotic liver disease (MASLD) and supplement GlucoRegulate is deserving of evaluation of its early-stage treatment. Link<\/a><\/li>\n\n\n\n
  2. Diets rich in glucose and fructose produce glycolytic overload in the liver, inducing mixed insulin resistance and providing the gateway for the path to development of type 2 diabetes. Link<\/a><\/li>\n\n\n\n
  3. The primary metabolic effect of fructose in the liver is to lift the restriction on flux of glucose metabolism by glucokinase regulatory protein (GKRP) and thereby facilitate glycolytic overload in the liver. Link<\/a><\/li>\n\n\n\n
  4. Hexokinase-2 linked glycolytic overload mediates diabetic embryopathy in an experimental model where supplement GlucoRegulate provides preventive therapy. Link<\/a><\/li>\n\n\n\n
  5. GlucoRegulate is a multi-modal dietary supplement primarlity acting through activation of Nrf2 with downstream health benefits linked to prevention of dicarbonyl stress, lipid peroxidation, oxidative stress, proteotoxicity and hyperglycemia-linked glycolytic overload. Downstream benefits were improved regulation of glucose and lipid metabolism and decreased inflammation, extracellular matrix remodeling and senescence markers. Link<\/a><\/li>\n<\/ol>\n\n\n\n

    Still much more to discover in 2026!<\/p>\n\n\n\n

    Paul J Thornalley, 26th December 2025.<\/p>\n\n\n\n

    New paper<\/h2>\n\n\n\n

    Naila Rabbani and Paul J Thornalley (2025) Molecular mechanisms of metabolic dysfunction-associated steatotic liver disease (MASLD): functional analysis of glucose and fructose metabolism pathways. Clinical Science 139, 1\u201325<\/strong>.<\/a><\/p>\n\n\n\n

    A pleasure to share this paper covering dietary glucose- and fructose-driven mechanisms of development of MASLD and in so doing, revealing the mechanism of development of insulin resistance and processes leading to peripheral insulin resistance and type 2 diabetes.<\/p>\n\n\n\n

    Summary points<\/strong><\/p>\n\n\n\n