Diabetes and metabolic disease are common condition of the West. The predominance of these diseases is rapidly increasing worldwide and is becoming a major health problem. (Kahn et al. 2006) Diabetes mellitus affected an estimated 285 million people worldwide in 2013 and is expected to affect 439 million people by 2030. (Shaw JE 2010)

The story of observing berberine’s (one of the bioactive compounds of Berberis vulgaris) antidiabetic effect started in the 80’s. The authors of a research (Yan-xia & An-qiang 1995) accidentally found it when berberine was used to treat diarrhoea for patients who suffered from diabetes.  According to that result, berberine was used to treat non-insulin dependent diabetes mellitus (NIDDM) during 1983 to 1987. (Yan-xia & An-qiang 1995)

 

What is pancreas and how does it work?

The pancreas, which is a retroperitoneal gland, lies posterior to the greater curvature of the stomach. This organ is made up of small clusters of glandular epithelial cells. There are two types of pancreatic cells: the dark-stained cells from acini, connected to ducts, and islet cells of light-stained clusters (Islet of Langehans). The cells in Islet of Langehans secrete a mixture of hormones (glucagon, insulin, somatostatin and pancreatic polypeptide – which help control blood sugar levels) providing endocrine function of the pancreas. (Tortora 2011)

The acinar cells secrete digestive enzymes (called pancreatic juice) into the pancreatic duct (duct of Wirsung). (Fehmann HC 1995)

Centroaciner cells take place in the lumen of the acinus (the origin of the secretory duct).

The lumen of the acinus leads into the intralobular ducts. These ducts are covered by low columnar epithelial cells. They look almost the same as centroacinar cells. In these areas, there are goblet cells and sometime argetaffin cells as well. Monoclonal antibodies of pancreas are reactive with acinar, ductal and islet cells.

In case of feeding and digestion the acinar cells go through cyclic morphological changes. The zymogen granule content of the cells is depleted after consuming a large amount of meal. Size of them decrease with number of granules. After depletion of these granules, the Golgi apparatus at the apex of the cell start expanding. The reductions in size and number of granules “occur with a substantial increase in pancreatic enzyme secretion”. (Feldman & Friedman 2010)

Causes of Pancreatic Disorders

 

In case of pancreatic problem pancreatic beta cells are damaged or become dysfunctional because of the oxidative stress, the persistently high glucose or lipid levels, inflammatory mediators released from the adipose tissue and endoplasmic reticulum. Oxidative stress and inflammation are proved to be critical for the pathogenesis. (Li 2014)

Regarding age range of patients, pancreatic diseases are increasingly recognized in the pediatric age group. The occurrence of acute pancreatitis, acute recurrent pancreatitis and chronic pancreatitis in case of children is getting the same amount as that of adults.

Although cystic fibrosis is still the most common cause of exocrine pancreatic insufficiency. “Other causes such as chronic pancreatitis may be as common as Shwachman-Diamond syndrome.” Long-term effects of pancreatic diseases (especially in cases of children) reflect the challenging life with nutritional deficiencies, pancreatogenic diabetes and potentially pancreatic cancer. (Uc & Fishman 2017)

Plants with berberine content as a traditional remedy for pancreas problems

About 1200 plants have been claimed to have compounds with antidiabetic properties, and over 400 plants and their bioactive compounds have been scientifically evaluated for type 2 diabetes treatment. (Kalasz 2011)

The effect of berberine on insulin secretion is controversial. Berberine is an isoquinoline alkaloid present in several plants, like Berberis spp. and Coptis spp. Berberine is a conventional component both in Chinese medicine and Ayurveda. It is also characterized by a diversity of pharmacological effects. (Imenshahidi and Hossenzadeh 2016)

Nowadays there is a noticeable growing scientific interest in its anti-diabetic action which seem to be increasingly prevalent among Western societies, thanks to its important role in activating AMP-activated protein kinase (AMPK). It is a key enzyme in metabolism.  (Xu and Xiao et al. 2014)

Conclusion

The majority of these studies (see references) investigated in this blog post suggests that there might be a significant benefit to patients with type 2 diabetes mellitus from treatment with berberine extract.

There were some adverse reactions reported like (minor digestive issues that tended to resolve 2 weeks in the study) by patients treated with type 2 diabetes mellitus.

Overall, these researches have concluded that berberine is a safe and effective therapy for improvement in insulin action but more studies should focus on human experiments to validate the metabolism-modulating and pancreas rejuvenating activities of berberine in vivo.

The inhibitory effect of barberry on oxidative stress was not observed in all the human researches.

As for these studies, only those patients can benefit where pancreas problems had not been occurred by stress as mental health factor.

Only two studies overviewed papers about pancreatic cell reproduction. The authors’ strategical approach for the prevention and treatment of diabetes was maintaining pancreatic beta cell function and increasing pancreatic beta cell mass to discover novel antidiabetics. (Sin Oh 2015; Cernea and Dobreanu 2013)

Although the evidence that berberine influences the recovery of pancreas islet beta-cells in animal research (Yan-xia & An-qiang et al. 1995) looks promising, further randomized, double blind active or placebo controlled research is imperative.

REFERENCES

American Diabetes Association. Available at: http://www.diabetes.org. Accessed: 13th November 2016.

Bergner, P. (2002). “Herbs and insulin resistance”. Medical Herbalism. A Journal for the Clinical Practitioner. Vol. 13, Number 2. Available at: http://medherb.com/bi/Issue-132-Winter-2002.pdf.pdf. Accessed: 2nd March 2017.

Bhutada, P.  et al. (2011). Protection of cholinergic and antioxidant system contributes to the effect of berberine ameliorating memory dysfunction in rat model of streptozotocin-induced diabetes. Behav Brain Res. 220(1):30-41. Available at: https://www.ncbi.nlm.nih.gov/pubmed/21262264. Accessed: 11th January 2017.

Chen. C. et al. (2010). Berberine inhibits PTP1B activity and mimics insulin action. Biochem Biophys Res Commun. Page 397-543.

Dong, H. & Wang, N. et al. (2012). Berberine in the treatment of type 2 diabetes mellitus: a systemic review and meta-analysis. Evidence-Based Complementary and Alternative Medicine. Vol. 2012. Article ID 591654. Available at:

https://www.scopus.com/record/display.uri?eid=2-s2.0-84868692016&origin=inward&txG

id=E8D9CC29BE491E8F24125BC40158A39A.wsnAw8kcdt7IPYLO0V48gA%3a2.

Accessed: 16th March 2017.

Fehmann, HC. & Goke R. et al. (1995). Cell and molecular biology of the incretin hormones glucagon-like peptide-I and glucose-dependent insulin-releasing polypeptide. Endorcrine Rev. Page 390-410.

Feldman, M. & Friedman, L. S. (2010). Sleisenger and Fordtran’s Gastrointestinal and Liver Disease. Saunders. Page 912-915.

Gu, Y. & Zhang, Y. et al. (2010) Effect of traditional Chinese medicine berberine on type 2 diabetes based on comprehensive metabonomics. Talanta. Elsevier. Page 766-772.

Házi Patika. A cukorbetegség 10 figyelmeztető tünete. Available at: http://www.hazipatika.com/napi_egeszseg/belgyogyaszat/cikkek/a_cukorbetegseg_10_figyelmezteto_tunete/20141211165030. Accessed: 4th November 2016.

Imenshahidi, M. and Hossenzadeh, H. (2016). Berberis Vulgaris and Berberine: An Update Review. Available at: https://www.ncbi.nlm.nih.gov/pubmed/27528198. Accessed: 22nd February 2017.

Kahn, S. E. & Hull, R. L. et al. (2006). Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature. Available at: http://www.nature.com/nature/journal/v444/n7121/full/nature05482.html?foxtrotcallback=true. Accessed: 21st January 2017.

Kalász, H. & Singh, J. et al. (2011). Medicinal chemistry of the anti-diabetic effects of momordica charantia: active constituents and modes of actions. Open Medicinal Chemistry Journal. Vol. 5. No. 2. Page 70-77.

Kashkooli, R. I. & Najafi, S. S. et al. (2015). The Effect of Berberis Vulgaris Extract on Transaminase Activities in Non- Alcoholic Fatty Liver Disease. Hepat Mon. DOI: 10.5812/hepatmon.25067.

Li, Z. & Geng, Y. N. et al. (2014). Antioxidant and anti-inflammatory activities of berberine in the treatment of diabetes mellitus. Evid Based Complement Alternative Medicine. Available at: https://www.ncbi.nlm.nih.gov/pubmed/?term=Oxidative+stress+and+inflammation

+are+proved+to+be+critical+for+the+pathogenesis+of+diabetes+mellitus. Accessed: 15th March 2017.

Mediline Plus. U.S. National Library of Medicine. Available at: https://medlineplus.gov/pancreaticdiseases.html. Accessed: 13th November 2016.

Pancreas.org. Available at: https://pancreas.org. 13th November 2016.

Park, SH. et al. (2015). Berberine induces apoptosis via ROS generation in PANC-1 and MIA-PaCa2 pancreatic cell lines. Braz J Med Biol Res. 48(2):111-9. Available at: https://www.ncbi.nlm.nih.gov/pubmed/25517919. Accessed: 12th January 2017.

Pérez-Rubio, KG & González-Ortiz, M. et al. (2013). Effect of berberine administration on metabolic syndrome, insulin sensitivity, and insulin secretion. Metab Syndr Relat Disord. Vol. 11. Issue 5. Page 366-369.

Pinto-Garcia, L. et al. (2010). Berberine inhibits cell growth and mediates caspase-independent cell death in human pancreatic cancer cells. Planta Med. Vol. 76. Issue 11. Page 1155-1161.

Schor, J. (2012). Clinical Applications for Berberine. Natural Medicine Journal. Vol. 4, Issue 12. Available at: http://www.naturalmedicinejournal.com/journal/2012-12/clinical-applications-berberine. Accessed: 11th January 2017.

Shaw, J. E. & Sicree, R. A. et al. (2010). Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. Available at: https://www.ncbi.nlm.nih.gov/pubmed/19896746. Accessed: 22nd January 2017.

Sin Oh, Y. (2015). Plant-Derived Compounds Targeting Pancreatic Beta Cells for the Treatment of Diabetes. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4637477. Accessed: 12th January 2017.

Tortora, G. J. & Derrickson, B. (2011). Principles of Anatomy and Physiology. John Wiley & Sons (Asia) Pte Ltd. (13th Edition) Page 988-990.

Uc, A. & Fishman, D. S. (2017). Pancreatic Disorders. Pediatr Clin North America. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28502446?_ga=2.27038200.435107471.1500806318-1772739099.1483732425. Accessed: 1st July 2017.

Webbeteg. Mi a cukorbetegség? A diabétesz típusai. Available at: http://www.webbeteg.hu/cikkek/cukorbetegseg/122/mi-a-cukorbetegseg. Accessed at: 4th November 2016.

Xu, M. & Yuanyuan, X. et al. (2014). Berberine Promotes Glucose Consumption Independently of AMP-Activated Protein Kinase Activation. Plos One. Avialable at: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0103702. Accessed: 11th May 2017.

Yan, H. & Xia, M. et al. (2015). Efficacy of Berberine in Patients with Non-Alcoholic Fatty Liver Disease. PLoS One. Available at: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0134172. Accessed: 14th May 2017.

Yan-xia & An-qiang et al. (1995). Therapeutic Effect of Berberine on 60 Patients with Non-Insulin Dependent Diabetes Mellitus and Experimental Research. Chinese Journal of Integrated Traditional Chinese and Western Medicine. Page 91-95.

Zhang, Y. (2008). Treatment of Type 2 Diabetes and Dyslipidemia with the Natural Plant Alkaloid Berberine. J Clin Endocrinol Metab.

Zhang and Li et al. (2008). Treatment of Type 2 Diabetes and Dyslipidemia with the Natural Plant Alkaloid Berberine. The Journal of Clinical Endocrinology & Metabolism. Vol. 93. Issue 7. Page 2559-2565.