Beta cell

New hormone stimulates pancreatic β-cell proliferation.

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Diabetes affects more than 360 million people worldwide and its prevalence is increasing, with 552 million diabetics predicted worldwide by 2030. Scientists recently discovered a hormone that could improve future diabetes management by stimulating replenishment of insulin-producing β cells in the pancreas.

The hormone, which has been named betatrophin, was discovered in studies of a mouse model of severe insulin resistance in which chemical blockade of insulin receptors induced pancreatic β-cell proliferation. Betatrophin was identified in murine liver and fat, and its stimulatory effect on cellular replication was limited to β cells. Its expression was also reported in human liver tissue.

Betatrophin treatment of mice increased proliferation of pancreatic β-cells by an average of 17-fold within a few days, causing an expansion of β-cell mass and increased insulin concentrations in the pancreas.

Betatrophin’s discovery “is a very exciting new development, and is only the beginning of the story”, says C Ronald Kahn (Joslin Diabetes Center, Boston, MA, USA). He adds that unanswered questions include whether “action on islets is direct or indirect. We don’t know how betatrophin works; is it only one growth factor or one of many? There is a lot of future work to be done”.

Senior author Douglas Melton (Harvard University, Cambridge, MA, USA) said: “It’s not often that one finds a new hormone, so it opens up all kinds of possibilities for new treatments”.

The most immediate application for betatrophin is for the “millions of prediabetics who are on their way to getting type 2 diabetes. If these individuals still have β cells, this hormone could give them more β cells and alleviate the need for insulin injections”, Melton continued. Betatrophin may also prove beneficial in type 1 diabetes, which is initiated by an autoimmune process. “If the disease is just starting, one could give an immunosuppressant and this hormone to forestall the onset of type 1 diabetes.”

Melton cautions that results from human studies should not be expected quickly. “We are currently working with our collaborators Evotec and Janssen to make the human betatrophin protein. This will take more than a year.” Results from studies in humans might be available “2—3 years from now, if all goes well”.

Source: Lancet

Phase 3 study: Canagliflozin improved beta cell function.

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An SGLT2 inhibitor recently approved by the FDA may improve measures of beta cell function in addition to glycemic control in patients already taking metformin plus sulfonylurea, according to phase 3 study results presented here at the AACE Annual Scientific and Clinical Congress.

“Despite the fact it doesn’t act directly on the beta cells, there is a lot of evidence from previous studies that SGLT2 inhibitors can improve beta-cell function,” David Polidori, PhD, of Janssen Research & Development, LLC, said here during a presentation.

Polidori and colleagues conducted a 26-week, randomized, double blind, placebo controlled study to evaluate canagliflozin (Invokana, Janssen) 100-mg and 300-mg compared with placebo as an add on to metformin plus sulfonylurea in patients with type 2 diabetes (n=469; mean age, 57 years). The mean baseline HbA1c level was 8.1%, BMI was 33 kg/m2, and duration of diabetes was 9.6 years, according to data.

Of the 469 patients, 168 were administered a meal tolerance test at baseline and week 26. Their plasma glucose and serum C-peptide levels were measured seven times over a 3-hour period.

Polidori reported that at week 26, canagliflozin 100 mg significantly reduced HbA1c by –0.71% and 300 mg  by –0.92% compared with placebo (P<.001).

Further data indicate that the insulin secretion rates (ISR) vs. glucose relationship did not change with placebo. However, the relationship shifted upwards in both canagliflozin doses, Polidori said. This indicated an increase in ISR at each plasma glucose concentration, according to data.

Measures of beta cell function, including the ratio of C-peptide to glucose, were approximately 20% higher than baseline levels in both canagliflozin groups (P=.051 for 100 mg and P=.056 for 300 mg) but remained relatively unchanged in the placebo group. Mean beta cell glucose sensitivity was also increased by about 20% in both canagliflozin groups (P=.14 for 100 mg andP=.22 for 300 mg).

Additionally, mean ISR at 9 mM of glucose increased by about 50% to 60% in both canagliflozin groups (P=.02 for 100 mg and P=.007 for 300 mg), but remained relatively unchanged in the placebo group.

“Consistent with what we’ve seen in patients at earlier stages of diabetes and in some of the animal studies, both doses of canagliflozin improved the measures of beta cell function that we looked at in the meal tolerance test in these more advanced patients who were already inadequately controlled on dual therapy. This is promising,” Polidori said. “This is 26-week data and we’re certainly interested to see longer term data to see if this type of treatment can better prolong beta cell function and hopefully slow the rate of progression of type 2 diabetes.” – by Samantha Costa

Source: Endocrine Today